perlecan

 

  • This could influence the gene expression profile of the cells, especially in their extracellular matrix, which often provides physical support and a chemical barrier for the
    cells.

  • [16] The protein becomes visible by immunostaining on day 15 during mouse development, independently from other basement membrane proteins, suggesting that it is simply a
    part of the ECM of developing chondrocytes, in addition to collagen II and other cartilage markers that are expressed starting on day 12.

  • The first study of perlecan expression during embryonal development found that the protein was first expressed during development of the cardiovascular system, and later correlates
    with maturation of the majority of tissues in the body, i.e.

  • In human coronary smooth muscle cells in culture, TGF-β1 signaling showed no effect on perlecan expression although it did upregulate other matrix constituents.

  • While studying the effect of proteoglycan composition on nephritic permselectivity, it was noted that puromycin treatment of human glomerular endothelial cells (HGEC) altered
    the sulfation level of GAG chains on proteoglycans such as perlecan, which in turn caused a decrease in the stability of the GAG chains.

  • [17] Signaling pathways and their effect on expression[edit] Signaling pathways function to elevate or decrease levels of transcription of genes, which in turn cause cells
    to change their gene expression profile.

  • One study examined the in vitro effects of pressure on global gene transcription using a microarray approach and a cell stretching system meant to simulate intraocular pressure
    in the lamina cribosa (connective tissue) of the optic nerve head.

  • By expressing a recombinant form of the N-terminal domain I of the protein and demonstrating that digestion of the peptide with either heparanase or chondroitinase did not
    lead to complete loss of the peptide’s activity, it was shown that chondroitin sulfate chains can be added to human perlecan.

  • As previously mentioned, to investigate the effect of brain inflammation on expression levels of perlecan, needle stab wounds were created in mice brains, and after inflammation
    and variable periods of recovery, mRNA and protein levels were assessed via in situ hybridization and immunostaining.

  • This difference between endothelial cells from the study in 2007 and the epithelial cell studied in these experiments is indicative of how varied the regulatory mechanisms
    of perlecan may be in different cell types.

  • [34] In the rat embryo, perlecan expression has been shown to increase in vascular smooth muscle cells (VSMCs) post e19 in fetal development.

  • The core protein mRNA levels of proteoglycans were not affected, thus the decrease in GAG chains was as a result of some other factor, which in this case turned out to be
    a decrease in expression of sulfate transferase enzymes, which play a key role in GAG biosynthesis.

  • In another study, hypoxia led to induction of genes associated with apoptosis and cell death, but repression of genes was not limited to proteins associated with a specific
    pathway.

  • [53] In the epidermal injury study, a wound spanning the depth of the epidermis was created in exon 3-negative mice and control mice, and in the knockout mice angiogenesis
    and the hallmarks of wound healing were slow to develop possibly due to decreased growth factor sequestration by the heparan sulfate-negative perlecan.

  • Cell stressors and their effect on expression[edit] Mechanical and chemical stress can damage basement membranes or the cells they support.

  • [67] This was first shown in colon cancer cell lines, and subsequently in cell lines of other tissue origins, but in each case intact STAT1 transcription factor was required
    for the signal to take effect.

  • These plaques induce a constant state of inflammation in areas of accumulation, leading to expression of certain inflammation-related gene products, some of which perpetuate
    the inflammation in the brain context.

  • In tissue engineered heart valves created by seeding myofibroblasts onto collagen type I followed by endothelial cells, heparan sulfate proteoglycan expression has been verified,
    although no distinction between syndecan and perlecan has been made in these tissues.

  • In vitro studies of TGF-β1 signaling and its effects on perlecan expression can have varying results in different cell types.

  • Function Perlecan is a key component of the extracellular matrix of cartilage[15] where it is essential for normal growth plate development and long bone growth.

  • This and perlecan’s role as endorepellin prompted one study into the nature of perlecan expression regulation by endothelial cells during hypoxic conditions.

  • Specific proteases act on the protein in the extracellular environment when cells have a reason to move or change their surroundings.

  • [77] A similar finding was shown in acetamenophin treatment of mice, where perlecan and other matrix components were heavily expressed in necrotic lesions of the liver.

  • The study showed that the exon 3 knockout mice had collapse of lens capsule integrity by postnatal week 3, indicating a role for the amino acids deleted from domain I of perlecan
    in maintaining lens capsule basement membrane integrity.

  • In this case, it seems that the molecule’s signaling function is the operative upregulated factor, especially due to the increase in sulfation of the heparan sulfate chains.

  • Perlecan is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis.

  • [70] When T84 intestinal epithelial cells are exposed to hypoxic conditions for 24 hours a significant increase in perlecan mRNA and protein production occurs.

  • Studies from gene knockout mice and human diseases have also revealed critical in vivo roles for perlecan in cartilage development[56] and neuromuscular junction activity.

  • Using a similar cell stretching mechanism to mimic arterial pressure, this investigation showed that perlecan production increased in response to mechanical strain.

  • This microvascular-specific regulation by VEGF165 raises the possibility that the anti-coagulant function of perlecan is a part of the damage-control process in brain endothelia.

  • A thorough study of perlecan expression during chick embryo development has shown that perlecan is present at the morula stage and for the rest of development, although expression
    can be transient and precisely timed in certain tissue predecessors.

  • Another system using a disorganized hydrated collagen I gel has been used to demonstrate that primary human corneal fibroblasts will eventually invade the gel and create a
    matrix consisting of collagen type I and perlecan, as well as several other sulfated matrix glycoproteins.

  • The perlecan transgenic mice, however, exhibited muscle hypertrophy,[55] indicating a role for perlecan in muscle development as well as in cartilage growth plate mediated
    long bone growth.

  • [52] This developmentally dynamic tissue showed a serious misregulation of extracellular matrix components including perlecan with TGF-β1 over expression.

  • Removal of HS chains may affect matrix organization and endothelial barrier function.

  • It could be that these endothelial cells merely downregulated transcription of many genes in response to hypoxic conditions.

  • A number of signaling molecules can effect changes in perlecan expression including the transforming growth factor-Beta (TGF-β), interleukin(IL) and vascular endothelial growth
    factor (VEGF) families of molecules.

  • Morpholinos were used to block translation of the perlecan mRNA in zebrafish embryos, as part of an investigation into perlecan function in skeletal and vascular development.

  • Spatio-temporal specificity in trans-activation of the perlecan gene during development is key to the maturation of basement membranes and thus to the complete separation
    of epithelia from endothelia and stroma.

  • [60] In vivo demonstration of the dynamic regulation of perlecan and its control by extracellular signaling pathways is critical to our understanding of the protein’s role
    in development.

  • [31] Expression Expression during development[edit] Timing of gene expression during development varies from tissue to tissue.

  • Addition of heparanase to cell culture of epithelia in basement membrane caused an increase in epithelial cell proliferation due to FGF-10 release.

  • This suggests that, in the exon 3 knockout, the remaining attachment sites for heparan sulfate on domains I and V available for FGF-2 binding[19] or the site on domain 3 available
    for FGF-18 binding[20] may be sufficient for normal long bone growth.

  • [14] Thus, perlecan core protein and HS chains could modulate matrix assembly, cell proliferation, lipoprotein binding and cell adhesion.

  • [40] Taken with the data,[41] that mice lacking the pln gene cannot maintain stable cartilage, it is apparent that perlecan is essential to the maturation and stability of
    cartilaginous structure.

  • Chemical damage to organs can affect not only the cell’s genetic and mechanical integrity but the extracellular matrix of the tissue.

  • In a mouse model of Alzheimer’s plaque formation, IL-1-alpha effects an increase in perlecan expression in response to brain injury.

  • [68] Presumably the loss of perlecan expression stems from downregulation of transcription via STAT1 transcription factor activity as shown previously.

  • [78] Expression in cell culture[edit] One of the resounding arguments against the validity of in vitro results of cell culture on 2D plastic plates is that the environment
    does not accurately reflect that of the cells in the organism.

  • These in vitro results are not necessarily representative of normal physiological interferon- γ concentrations, nor are the cytokine normally expressed widely but instead
    at very specific developmental timepoints.

  • The end effect of signaling pathways is exerted on the promoter of genes, which can include elements upstream or downstream of the transcriptional start site, some of which
    can exist inside of the transcribed gene itself.

  • [72] At the organismic level, mechanical stress has a profound impact on extracellular matrix integrity and probably causes induction of a number of ECM genes for repair and
    remodeling of ECM in tissue stroma and basement membranes.

  • [29] This proteolytic process may have significance in disease as a corresponding fragment was found in the urine of patients suffering end-stage renal failure[30] and in
    the amniotic fluid of pregnant women who have undergone premature rupture of the membrane.

  • [69] Under hypoxic conditions, this study found that perlecan expression by rat cardiac microvascular endothelial cells was decreased sixty-one percent compared to normal
    controls.

  • This resulted in the cartilage-compromised phenotype previously discussed and loss of basement membrane integrity in a variety of tissues.

  • Later embryonic development is just as precisely regulated as pre-implantation development, and is more complicated due to differentiation of all tissues.

  • Perlecan is also a key component of the vascular extracellular matrix, where it interacts with a variety of other matrix components and helps to maintain the endothelial barrier
    function.

  • [38] Perlecan also showed nerve adhesive properties in a previous study, further suggesting that it may act in an attractive role in combination with laminin rather than a
    repulsive one.

  • [13] Although HS chains are not required for correct folding and secretion of the protein, lack of HS or decreased sulfation can decrease perlecan’s ability to interact with
    matrix proteins.

  • This is supported by a study showing that knockdown of perlecan production inhibits the final stages of chondrogenic differentiation in C3H10T1/2 fibroblasts in culture.

  • [80] This effect also led to a lack of hemidesmosomes in the developing tissue.

  • [39] Cartilage and bone development have proven to be dependent upon perlecan expression.

  • Perlecan isolated from developing growth plates has been shown to bind to FGF-2 via its heparan sulfate side chains,[19] and to FGF-18 via domain III of its core protein[20]
    and mediates their action on FGF receptors.

  • [54] The collagen type II promoter allowed perlecan expression in the extracellular matrix made by chondrocytes only but not in the basement membranes made by endothelial,
    epithelial or muscle cells.

  • It does seem counterintuitive that endothelial cells would proliferate less quickly due to loss of perlecan and its endorepellin subunit.

  • Perlecan was originally isolated from a tumor cell line and shown to be present in all native basement membranes.

  • Perlecan and laminin-1 appear to be important in this guidance pathway, although perlecan induction occurs slightly later than laminin-1.

 

Works Cited

[‘1. GRCh38: Ensembl release 89: ENSG00000142798 – Ensembl, May 2017
2. ^ Jump up to:a b c GRCm38: Ensembl release 89: ENSMUSG00000028763 – Ensembl, May 2017
3. ^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National
Library of Medicine.
4. ^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Jump up to:a b Noonan DM, Fulle A, Valente P, Cai S, Horigan E, Sasaki M, et al. (December 1991). “The
complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule”. The Journal of Biological Chemistry. 266
(34): 22939–47. doi:10.1016/S0021-9258(18)54445-8. PMID 1744087.
6. ^ Jump up to:a b Arikawa-Hirasawa E, Wilcox WR, Le AH, Silverman N, Govindraj P, Hassell JR, Yamada Y (April 2001). “Dyssegmental dysplasia, Silverman-Handmaker type, is caused
by functional null mutations of the perlecan gene”. Nature Genetics. 27 (4): 431–4. doi:10.1038/86941. PMID 11279527. S2CID 22934192.
7. ^ “Entrez Gene: HSPG2 heparan sulfate proteoglycan 2”.
8. ^ Kallunki P, Eddy RL, Byers MG, Kestilä M, Shows
TB, Tryggvason K (October 1991). “Cloning of human heparan sulfate proteoglycan core protein, assignment of the gene (HSPG2) to 1p36.1—-p35 and identification of a BamHI restriction fragment length polymorphism”. Genomics. 11 (2): 389–96. doi:10.1016/0888-7543(91)90147-7.
PMID 1685141.
9. ^ Jump up to:a b Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC, Francomano CA, et al. (May 2002). “Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia”.
American Journal of Human Genetics. 70 (5): 1368–75. doi:10.1086/340390. PMC 447613. PMID 11941538.
10. ^ Jump up to:a b Hassell JR, Robey PG, Barrach HJ, Wilczek J, Rennard SI, Martin GR (August 1980). “Isolation of a heparan sulfate-containing
proteoglycan from basement membrane”. Proceedings of the National Academy of Sciences of the United States of America. 77 (8): 4494–8. Bibcode:1980PNAS…77.4494H. doi:10.1073/pnas.77.8.4494. PMC 349870. PMID 6449008.
11. ^ Jump up to:a b Iozzo
RV (April 1994). “Perlecan: a gem of a proteoglycan”. Matrix Biology. 14 (3): 203–8. doi:10.1016/0945-053X(94)90183-X. PMID 7921536.
12. ^ Aaron L Fidler, Carl E Darris, Sergei V Chetyrkin, Vadim K Pedchenko, Sergei P Boudko, Kyle L Brown, W Gray
Jerome, Julie K Hudson, Antonis Rokas, Billy G Hudson (2017) Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues eLife 6:e24176 https://doi.org/10.7554/eLife.24176
13. ^ Jump up to:a b c Dolan M, Horchar T, Rigatti B,
Hassell JR (February 1997). “Identification of sites in domain I of perlecan that regulate heparan sulfate synthesis”. The Journal of Biological Chemistry. 272 (7): 4316–22. doi:10.1074/jbc.272.7.4316. PMID 9020150.
14. ^ Jump up to:a b Tapanadechopone
P, Hassell JR, Rigatti B, Couchman JR (November 1999). “Localization of glycosaminoglycan substitution sites on domain V of mouse perlecan”. Biochemical and Biophysical Research Communications. 265 (3): 680–90. doi:10.1006/bbrc.1999.1714. PMID 10600481.
15. ^
Jump up to:a b SundarRaj N, Fite D, Ledbetter S, Chakravarti S, Hassell JR (July 1995). “Perlecan is a component of cartilage matrix and promotes chondrocyte attachment”. J. Cell Sci. 108 ( Pt 7) (7): 2663–72. doi:10.1242/jcs.108.7.2663. PMID 7593307.
16. ^
Jump up to:a b c d e Arikawa-Hirasawa E, Watanabe H, Takami H, Hassell JR, Yamada Y (1999). “Perlecan is essential for cartilage and cephalic development”. Nat. Genet. 23 (3): 354–8. doi:10.1038/15537. PMID 10545953. S2CID 20871336.
17. ^ Jump up
to:a b Hassell J, Yamada Y, Arikawa-Hirasawa E (2002). “Role of perlecan in skeletal development and diseases”. Glycoconj. J. 19 (4–5): 263–7. doi:10.1023/A:1025340215261. PMID 12975604. S2CID 6832133.
18. ^ Jump up to:a b Tavormina PL, Shiang R,
Thompson LM, Zhu YZ, Wilkin DJ, Lachman RS, et al. (March 1995). “Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3”. Nature Genetics. 9 (3): 321–8. doi:10.1038/ng0395-321. PMID 7773297. S2CID
10050610.
19. ^ Jump up to:a b c Smith SM, West LA, Govindraj P, Zhang X, Ornitz DM, Hassell JR (April 2007). “Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors”. Matrix Biology. 26 (3):
175–84. doi:10.1016/j.matbio.2006.10.012. PMID 17169545.
20. ^ Jump up to:a b c Smith SM, West LA, Hassell JR (December 2007). “The core protein of growth plate perlecan binds FGF-18 and alters its mitogenic effect on chondrocytes”. Archives of
Biochemistry and Biophysics. 468 (2): 244–51. doi:10.1016/j.abb.2007.10.006. PMC 2696159. PMID 17971291.
21. ^ West L, Govindraj P, Koob TJ, Hassell JR (June 2006). “Changes in perlecan during chondrocyte differentiation in the fetal bovine rib
growth plate”. J. Orthop. Res. 24 (6): 1317–26. doi:10.1002/jor.20160. PMID 16705694. S2CID 2487979.
22. ^ French MM, Gomes RR, Timpl R, Höök M, Czymmek K, Farach-Carson MC, Carson DD (January 2002). “Chondrogenic activity of the heparan sulfate
proteoglycan perlecan maps to the N-terminal domain I”. J. Bone Miner. Res. 17 (1): 48–55. doi:10.1359/jbmr.2002.17.1.48. PMC 1774590. PMID 11771669.
23. ^ Kokenyesi R, Silbert JE (June 1995). “Formation of heparan sulfate or chondroitin/dermatan
sulfate on recombinant domain I of mouse perlecan expressed in Chinese hamster ovary cells”. Biochem. Biophys. Res. Commun. 211 (1): 262–7. doi:10.1006/bbrc.1995.1805. PMID 7779094.
24. ^ Björnson A, Moses J, Ingemansson A, Haraldsson B, Sörensson
J (April 2005). “Primary human glomerular endothelial cells produce proteoglycans, and puromycin affects their posttranslational modification”. Am. J. Physiol. Renal Physiol. 288 (4): F748–56. doi:10.1152/ajprenal.00202.2004. PMID 15585670. S2CID
13731498.
25. ^ Liuzzo JP, Petanceska SS, Moscatelli D, Devi LA (May 1999). “Inflammatory mediators regulate cathepsin S in macrophages and microglia: A role in attenuating heparan sulfate interactions”. Mol. Med. 5 (5): 320–33. doi:10.1007/BF03402068.
PMC 2230418. PMID 10390548.
26. ^ Whitelock JM, Murdoch AD, Iozzo RV, Underwood PA (April 1996). “The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin,
and heparanases”. J. Biol. Chem. 271 (17): 10079–86. doi:10.1074/jbc.271.17.10079. PMID 8626565. S2CID 8872716.
27. ^ Patel VN, Knox SM, Likar KM, Lathrop CA, Hossain R, Eftekhari S, Whitelock JM, Elkin M, Vlodavsky I, Hoffman MP (December 2007).
“Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis”. Development. 134 (23): 4177–86. doi:10.1242/dev.011171. PMID 17959718. S2CID 25819221.
28. ^ Li W, He H, Kuo CL,
Gao Y, Kawakita T, Tseng SC (June 2006). “Basement membrane dissolution and reassembly by limbal corneal epithelial cells expanded on amniotic membrane”. Invest. Ophthalmol. Vis. Sci. 47 (6): 2381–9. doi:10.1167/iovs.05-1491. PMC 1569675. PMID 16723447.
29. ^
Gonzalez EM, Reed CC, Bix G, Fu J, Zhang Y, Gopalakrishnan B, Greenspan DS, Iozzo RV (February 2005). “BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan”. J. Biol. Chem. 280 (8): 7080–7. doi:10.1074/jbc.M409841200.
PMID 15591058. S2CID 35841044.
30. ^ Oda O, Shinzato T, Ohbayashi K, Takai I, Kunimatsu M, Maeda K, Yamanaka N (November 1996). “Purification and characterization of perlecan fragment in urine of end-stage renal failure patients”. Clin. Chim. Acta.
255 (2): 119–32. doi:10.1016/0009-8981(96)06395-4. PMID 8937755.
31. ^ Vuadens F, Benay C, Crettaz D, Gallot D, Sapin V, Schneider P, Bienvenut WV, Lémery D, Quadroni M, Dastugue B, Tissot JD (August 2003). “Identification of biologic markers of
the premature rupture of fetal membranes: proteomic approach”. Proteomics. 3 (8): 1521–5. doi:10.1002/pmic.200300455. PMID 12923777. S2CID 5868882.
32. ^ Smith SE, French MM, Julian J, Paria BC, Dey SK, Carson DD (April 1997). “Expression of heparan
sulfate proteoglycan (perlecan) in the mouse blastocyst is regulated during normal and delayed implantation”. Dev. Biol. 184 (1): 38–47. doi:10.1006/dbio.1997.8521. PMID 9142982.
33. ^ Handler M, Yurchenco PD, Iozzo RV (October 1997). “Developmental
expression of perlecan during murine embryogenesis”. Dev. Dyn. 210 (2): 130–45. doi:10.1002/(SICI)1097-0177(199710)210:2
<130::AID-AJA6>3.0.CO;2-H. PMID 9337134.
34. ^ Soulintzi N, Zagris N (2007). “Spatial and temporal expression of perlecan in the early chick embryo”. Cells Tissues Organs (Print). 186 (4): 243–56. doi:10.1159/000107948. PMID 17785960. S2CID 41008675.
35. ^ Jump
up to:a b Weiser MC, Belknap JK, Grieshaber SS, Kinsella MG, Majack RA (November 1996). “Developmental regulation of perlecan gene expression in aortic smooth muscle cells”. Matrix Biol. 15 (5): 331–40. doi:10.1016/S0945-053X(96)90136-5. PMID
8981329.
36. ^ Jump up to:a b Belknap JK, Weiser-Evans MC, Grieshaber SS, Majack RA, Stenmark KR (January 1999). “Relationship between perlecan and tropoelastin gene expression and cell replication in the developing rat pulmonary vasculature”.
Am. J. Respir. Cell Mol. Biol. 20 (1): 24–34. CiteSeerX 10.1.1.327.6391. doi:10.1165/ajrcmb.20.1.3321. PMID 9870914.
37. ^ Shay EL, Greer CA, Treloar HB (July 2008). “Dynamic expression patterns of ECM molecules in the developing mouse olfactory
pathway”. Dev. Dyn. 237 (7): 1837–50. doi:10.1002/dvdy.21595. PMC 2787191. PMID 18570250.
38. ^ Key B, Treloar HB, Wangerek L, Ford MD, Nurcombe V (March 1996). “Expression and localization of FGF-1 in the developing rat olfactory system”. J.
Comp. Neurol. 366 (2): 197–206. doi:10.1002/(SICI)1096-9861(19960304)366:2
<197::AID-CNE1>3.0.CO;2-0. PMID 8698881. S2CID 38919059.
39. ^ Braunewell KH, Pesheva P, McCarthy JB, Furcht LT, Schmitz B, Schachner M (April 1995). “Functional involvement of sciatic nerve-derived versican- and decorin-like molecules and other chondroitin
sulphate proteoglycans in ECM-mediated cell adhesion and neurite outgrowth”. Eur. J. Neurosci. 7 (4): 805–14. doi:10.1111/j.1460-9568.1995.tb00683.x. PMID 7620627. S2CID 21088798.
40. ^ Jump up to:a b French MM, Smith SE, Akanbi K, Sanford
T, Hecht J, Farach-Carson MC, Carson DD (May 1999). “Expression of the heparan sulfate proteoglycan, perlecan, during mouse embryogenesis and perlecan chondrogenic activity in vitro”. J. Cell Biol. 145 (5): 1103–15. doi:10.1083/jcb.145.5.1103.
PMC 2133131. PMID 10352025.
41. ^ Jump up to:a b c d Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fässler R (November 1999). “Perlecan maintains the integrity of cartilage and some basement membranes”.
J. Cell Biol. 147 (5): 1109–22. doi:10.1083/jcb.147.5.1109. PMC 2169352. PMID 10579729.
42. ^ Gomes RR, Joshi SS, Farach-Carson MC, Carson DD (February 2006). “Ribozyme-mediated perlecan knockdown impairs chondrogenic differentiation of
C3H10T1/2 fibroblasts”. Differentiation. 74 (1): 53–63. doi:10.1111/j.1432-0436.2005.00055.x. PMC 1403289. PMID 16466400.
43. ^ Brown AJ, Alicknavitch M, D’Souza SS, Daikoku T, Kirn-Safran CB, Marchetti D, Carson DD, Farach-Carson MC (October
2008). “Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation”. Bone. 43 (4): 689–99. doi:10.1016/j.bone.2008.05.022. PMC 2621444. PMID 18589009.
44. ^ Gomes RR, Van Kuppevelt
TH, Farach-Carson MC, Carson DD (December 2006). “Spatiotemporal distribution of heparan sulfate epitopes during murine cartilage growth plate development”. Histochem. Cell Biol. 126 (6): 713–22. doi:10.1007/s00418-006-0203-4. PMID 16835755.
S2CID 13223192.
45. ^ Manton KJ, Leong DF, Cool SM, Nurcombe V (November 2007). “Disruption of heparan and chondroitin sulfate signaling enhances mesenchymal stem cell-derived osteogenic differentiation via bone morphogenetic protein signaling
pathways”. Stem Cells. 25 (11): 2845–54. doi:10.1634/stemcells.2007-0065. PMID 17702986. S2CID 24843235.
46. ^ Jump up to:a b Zoeller JJ, McQuillan A, Whitelock J, Ho SY, Iozzo RV (April 2008). “A central function for perlecan in skeletal
muscle and cardiovascular development”. J. Cell Biol. 181 (2): 381–94. doi:10.1083/jcb.200708022. PMC 2315682. PMID 18426981.
47. ^ Jump up to:a b Zoeller JJ, Whitelock JM, Iozzo RV (May 2009). “Perlecan regulates developmental angiogenesis
by modulating the VEGF-VEGFR2 axis”. Matrix Biol. 28 (5): 284–91. doi:10.1016/j.matbio.2009.04.010. PMC 2705690. PMID 19422911.
48. ^ Girós A, Morante J, Gil-Sanz C, Fairén A, Costell M (2007). “Perlecan controls neurogenesis in the developing
telencephalon”. BMC Dev. Biol. 7: 29. doi:10.1186/1471-213X-7-29. PMC 1852307. PMID 17411441.
49. ^ Jump up to:a b Rossi M, Morita H, Sormunen R, Airenne S, Kreivi M, Wang L, Fukai N, Olsen BR, Tryggvason K, Soininen R (January 2003). “Heparan
sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney”. EMBO J. 22 (2): 236–45. doi:10.1093/emboj/cdg019. PMC 140094. PMID 12514129.
50. ^ Morita H, Yoshimura A, Inui K, Ideura T, Watanabe H, Wang L, Soininen
R, Tryggvason K (June 2005). “Heparan sulfate of perlecan is involved in glomerular filtration”. Journal of the American Society of Nephrology. 16 (6): 1703–1710. doi:10.1681/ASN.2004050387. ISSN 1046-6673. PMID 15872080. S2CID 29638221.
51. ^
Jump up to:a b Srinivasan Y, Lovicu FJ, Overbeek PA (February 1998). “Lens-specific expression of transforming growth factor beta1 in transgenic mice causes anterior subcapsular cataracts”. J. Clin. Invest. 101 (3): 625–34. doi:10.1172/JCI1360.
PMC 508606. PMID 9449696.
52. ^ Jump up to:a b Flügel-Koch C, Ohlmann A, Piatigorsky J, Tamm ER (October 2002). “Disruption of anterior segment development by TGF-beta1 overexpression in the eyes of transgenic mice”. Dev. Dyn. 225 (2): 111–25.
doi:10.1002/dvdy.10144. PMID 12242711. S2CID 8607827.
53. ^ Zhou Z, Wang J, Cao R, Morita H, Soininen R, Chan KM, Liu B, Cao Y, Tryggvason K (July 2004). “Impaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan
heparan sulfate-deficient mice”. Cancer Res. 64 (14): 4699–702. doi:10.1158/0008-5472.CAN-04-0810. PMID 15256433. S2CID 2295597.
54. ^ Ishijima M, Suzuki N, Hozumi K, Matsunobu T, Kosaki K, Kaneko H, Hassell JR, Arikawa-Hirasawa E, Yamada
Y (May 2012). “Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation”. Matrix Biology. 31 (4): 234–245. doi:10.1016/j.matbio.2012.02.006. ISSN 0945-053X. PMC 3340529. PMID 22421594.
55. ^ Xu
Z, Ichikawa N, Kosaki K, Yamada Y, Sasaki T, Sakai LY, Kurosawa H, Hattori N, Arikawa-Hirasawa E (July 2010). “Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition”. Matrix
Biology. 29 (6): 461–470. doi:10.1016/j.matbio.2010.06.001. ISSN 0945-053X. PMC 2939214. PMID 20541011.
56. ^ Gomes RR, Farach-Carson MC, Carson DD (2004). “Perlecan functions in chondrogenesis: insights from in vitro and in vivo models”.
Cells Tissues Organs (Print). 176 (1–3): 79–86. doi:10.1159/000075029. PMID 14745237. S2CID 35356003.
57. ^ Iozzo RV, Pillarisetti J, Sharma B, Murdoch AD, Danielson KG, Uitto J, Mauviel A (February 1997). “Structural and functional characterization
of the human perlecan gene promoter. Transcriptional activation by transforming growth factor-beta via a nuclear factor 1-binding element”. J. Biol. Chem. 272 (8): 5219–28. doi:10.1074/jbc.272.8.5219. PMID 9030592. S2CID 23851324.
58. ^
Dodge GR, Kovalszky I, Hassell JR, Iozzo RV (October 1990). “Transforming growth factor beta alters the expression of heparan sulfate proteoglycan in human colon carcinoma cells”. J. Biol. Chem. 265 (29): 18023–9. doi:10.1016/S0021-9258(18)38265-6.
PMID 1698783.
59. ^ Morris JE, Gaza G, Potter SW (February 1994). “Specific stimulation of basal lamina heparan sulfate proteoglycan in mouse uterine epithelium by Matrigel and by transforming growth factor-beta 1”. In Vitro Cell. Dev. Biol.
Anim. 30A (2): 120–8. doi:10.1007/BF02631404. PMID 8012654. S2CID 6254328.
60. ^ Schmidt A, Lorkowski S, Seidler D, Breithardt G, Buddecke E (July 2006). “TGF-beta1 generates a specific multicomponent extracellular matrix in human coronary
SMC”. Eur. J. Clin. Invest. 36 (7): 473–82. doi:10.1111/j.1365-2362.2006.01658.x. PMID 16796604. S2CID 8803052.
61. ^ Jump up to:a b García de Yébenes E, Ho A, Damani T, Fillit H, Blum M (August 1999). “Regulation of the heparan sulfate
proteoglycan, perlecan, by injury and interleukin-1alpha”. J. Neurochem. 73 (2): 812–20. doi:10.1046/j.1471-4159.1999.0730812.x. PMID 10428080. S2CID 14191496.
62. ^ Hashimoto-Uoshima M, Noguchi K, Suzuki M, Murata A, Yanagishita M, Ishikawa
I (February 2002). “Effects of interleukin-4 on proteoglycan accumulation in human gingival fibroblasts”. J. Periodont. Res. 37 (1): 42–9. doi:10.1034/j.1600-0765.2002.00642.x. PMID 11842937.
63. ^ Tufvesson E, Westergren-Thorsson G (March
2000). “Alteration of proteoglycan synthesis in human lung fibroblasts induced by interleukin-1beta and tumor necrosis factor-alpha”. J. Cell. Biochem. 77 (2): 298–309. doi:10.1002/(SICI)1097-4644(20000501)77:2
<298::AID-JCB12>3.0.CO;2-D. PMID 10723095. S2CID 40207474.
64. ^ Kaji T, Yamamoto C, Oh-i M, Fujiwara Y, Yamazaki Y, Morita T, Plaas AH, Wight TN (September 2006). “The vascular endothelial growth factor VEGF165 induces perlecan synthesis via VEGF receptor-2
in cultured human brain microvascular endothelial cells”. Biochim. Biophys. Acta. 1760 (9): 1465–74. doi:10.1016/j.bbagen.2006.06.010. PMID 16914267.
65. ^ Llorente A, Prydz K, Sprangers M, Skretting G, Kolset SO, Sandvig K (January
2001). “Proteoglycan synthesis is increased in cells with impaired clathrin-dependent endocytosis”. J. Cell Sci. 114 (Pt 2): 335–43. doi:10.1242/jcs.114.2.335. PMID 11148135.
66. ^ Menne J, Park JK, Boehne M, Elger M, Lindschau C, Kirsch
T, Meier M, Gueler F, Fiebeler A, Bahlmann FH, Leitges M, Haller H (August 2004). “Diminished loss of proteoglycans and lack of albuminuria in protein kinase C-alpha-deficient diabetic mice”. Diabetes. 53 (8): 2101–9. doi:10.2337/diabetes.53.8.2101.
PMID 15277392.
67. ^ Jump up to:a b Sharma B, Iozzo RV (February 1998). “Transcriptional silencing of perlecan gene expression by interferon-gamma”. J. Biol. Chem. 273 (8): 4642–6. doi:10.1074/jbc.273.8.4642. PMID 9468523. S2CID 24591048.
68. ^
Fontana V, Choren V, Vauthay L, Calvo JC, Calvo L, Cameo M (December 2004). “Exogenous interferon-gamma alters murine inner cell mass and trophoblast development. Effect on the expression of ErbB1, ErbB4 and heparan sulfate proteoglycan
(perlecan)”. Reproduction. 128 (6): 717–25. doi:10.1530/rep.1.00335. PMID 15579589.
69. ^ Li YZ, Liu XH, Cai LR (April 2007). “Down-regulation of perlecan expression contributes to the inhibition of rat cardiac microvascular endothelial
cell proliferation induced by hypoxia”. Sheng Li Xue Bao. 59 (2): 221–6. PMID 17437047.
70. ^ Jin K, Mao XO, Eshoo MW, del Rio G, Rao R, Chen D, Simon RP, Greenberg DA (October 2002). “cDNA microarray analysis of changes in gene expression
induced by neuronal hypoxia in vitro”. Neurochem. Res. 27 (10): 1105–12. doi:10.1023/A:1020913123054. PMID 12462408. S2CID 7688503.
71. ^ Furuta GT, Dzus AL, Taylor CT, Colgan SP (August 2000). “Parallel induction of epithelial surface-associated
chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation”. J. Leukoc. Biol. 68 (2): 251–9. doi:10.1189/jlb.68.2.251. PMID 10947070. S2CID 17526437.
72. ^ Snow AD, Sekiguchi R, Nochlin D, Fraser P, Kimata
K, Mizutani A, Arai M, Schreier WA, Morgan DG (January 1994). “An important role of heparan sulfate proteoglycan (Perlecan) in a model system for the deposition and persistence of fibrillar A beta-amyloid in rat brain”. Neuron. 12 (1):
219–34. doi:10.1016/0896-6273(94)90165-1. PMID 8292358. S2CID 39006966.
73. ^ Kirwan RP, Fenerty CH, Crean J, Wordinger RJ, Clark AF, O’Brien CJ (2005). “Influence of cyclical mechanical strain on extracellular matrix gene expression
in human lamina cribrosa cells in vitro”. Mol. Vis. 11: 798–810. PMID 16205625.
74. ^ Baker AB, Ettenson DS, Jonas M, Nugent MA, Iozzo RV, Edelman ER (August 2008). “Endothelial cells provide feedback control for vascular remodeling
through a mechanosensitive autocrine TGF-beta signaling pathway”. Circ. Res. 103 (3): 289–97. doi:10.1161/CIRCRESAHA.108.179465. PMC 2766078. PMID 18583708.
75. ^ Morita N, Iizuka K, Murakami T, Kawaguchi H (July 2004). “N-terminal kinase,
and c-Src are activated in human aortic smooth muscle cells by pressure stress”. Mol. Cell. Biochem. 262 (1–2): 71–8. doi:10.1023/B:MCBI.0000038218.09259.1c. PMID 15532711. S2CID 23799480.
76. ^ Lee RT, Yamamoto C, Feng Y, Potter-Perigo
S, Briggs WH, Landschulz KT, Turi TG, Thompson JF, Libby P, Wight TN (April 2001). “Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells”. J. Biol. Chem. 276 (17):
13847–51. doi:10.1074/jbc.M010556200. PMID 11278699. S2CID 46310253.
77. ^ Gallai M, Kovalszky I, Knittel T, Neubauer K, Armbrust T, Ramadori G (May 1996). “Expression of extracellular matrix proteoglycans perlecan and decorin in carbon-tetrachloride-injured
rat liver and in isolated liver cells”. Am. J. Pathol. 148 (5): 1463–71. PMC 1861584. PMID 8623917.
78. ^ Cozma LG, Alexa ID, Dobrescu G (2004). “[Transcriptional and electron microscopic analysis of extracellular matrix proteoglycans
in acute acetaminophen intoxication]”. Rev Med Chir Soc Med Nat Iasi (in Romanian). 108 (2): 452–7. PMID 15688831.
79. ^ Stark HJ, Baur M, Breitkreutz D, Mirancea N, Fusenig NE (May 1999). “Organotypic keratinocyte cocultures in defined
medium with regular epidermal morphogenesis and differentiation”. J. Invest. Dermatol. 112 (5): 681–91. doi:10.1046/j.1523-1747.1999.00573.x. PMID 10233757.
80. ^ Breitkreutz D, Mirancea N, Schmidt C, Beck R, Werner U, Stark HJ, Gerl
M, Fusenig NE (May 2004). “Inhibition of basement membrane formation by a nidogen-binding laminin gamma1-chain fragment in human skin-organotypic cocultures”. J. Cell Sci. 117 (Pt 12): 2611–22. doi:10.1242/jcs.01127. PMID 15159456. S2CID
1421123.
81. ^ Ren R, Hutcheon AE, Guo XQ, Saeidi N, Melotti SA, Ruberti JW, Zieske JD, Trinkaus-Randall V (October 2008). “Human primary corneal fibroblasts synthesize and deposit proteoglycans in long-term 3-D cultures”. Dev. Dyn.
237 (10): 2705–15. doi:10.1002/dvdy.21606. PMC 3760227. PMID 18624285.
82. ^ Rothenburger M, Völker W, Vischer P, Glasmacher B, Scheld HH, Deiwick M (December 2002). “Ultrastructure of proteoglycans in tissue-engineered cardiovascular
structures”. Tissue Eng. 8 (6): 1049–56. doi:10.1089/107632702320934146. PMID 12542950.
83. ^ Ohji M, SundarRaj N, Hassell JR, Thoft RA (February 1994). “Basement membrane synthesis by human corneal epithelial cells in vitro”. Invest.
Ophthalmol. Vis. Sci. 35 (2): 479–85. PMID 8112997.
84. ^ Pradhan S, Zhang C, Jia X, Carson DD, Witt R, Farach-Carson MC (April 2009). “Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro”. Tissue Eng Part A.
15 (11): 3309–20. doi:10.1089/ten.TEA.2008.0669. PMC 2792055. PMID 19382872.
85. ^ Cohen IR, Murdoch AD, Naso MF, Marchetti D, Berd D, Iozzo RV (November 1994). “Abnormal expression of perlecan proteoglycan in metastatic melanomas”.
Cancer Res. 54 (22): 5771–4. PMID 7954396.
86. ^ Marchetti D, Menter D, Jin L, Nakajima M, Nicolson GL (October 1993). “Nerve growth factor effects on human and mouse melanoma cell invasion and heparanase production”. Int. J. Cancer.
55 (4): 692–9. doi:10.1002/ijc.2910550430. PMID 8407001. S2CID 25459596.
87. ^ Davies EJ, Blackhall FH, Shanks JH, David G, McGown AT, Swindell R, Slade RJ, Martin-Hirsch P, Gallagher JT, Jayson GC (August 2004). “Distribution and clinical
significance of heparan sulfate proteoglycans in ovarian cancer”. Clin. Cancer Res. 10 (15): 5178–86. doi:10.1158/1078-0432.CCR-03-0103. PMID 15297422. S2CID 396257.
88. ^ Kodama J, Shinyo Y, Kusumoto T, Seki N, Nakamura K, Hongo A,
Hiramatsu Y (July 2005). “Loss of basement membrane heparan sulfate expression is associated with pelvic lymph node metastasis in invasive cervical cancer”. Oncol. Rep. 14 (1): 89–92. doi:10.3892/or.14.1.89 (inactive 31 January 2024).
PMID 15944773.
89. ^ Jiang X, Multhaupt H, Chan E, Schaefer L, Schaefer RM, Couchman JR (December 2004). “Essential contribution of tumor-derived perlecan to epidermal tumor growth and angiogenesis”. J. Histochem. Cytochem. 52 (12):
1575–90. doi:10.1369/jhc.4A6353.2004. PMID 15557212. S2CID 30223615.
90. ^ Sharma B, Handler M, Eichstetter I, Whitelock JM, Nugent MA, Iozzo RV (October 1998). “Antisense targeting of perlecan blocks tumor growth and angiogenesis in
vivo”. J. Clin. Invest. 102 (8): 1599–608. doi:10.1172/JCI3793. PMC 509011. PMID 9788974.
91. ^ Aviezer D, Iozzo RV, Noonan DM, Yayon A (April 1997). “Suppression of autocrine and paracrine functions of basic fibroblast growth factor
by stable expression of perlecan antisense cDNA”. Mol. Cell. Biol. 17 (4): 1938–46. doi:10.1128/MCB.17.4.1938. PMC 232040. PMID 9121441.
92. ^ Jump up to:a b Marchisone C, Del Grosso F, Masiello L, Prat M, Santi L, Noonan DM (2000).
“Phenotypic alterations in Kaposi’s sarcoma cells by antisense reduction of perlecan”. Pathol. Oncol. Res. 6 (1): 10–7. doi:10.1007/BF03032652. PMID 10749582. S2CID 10863998.
93. ^ Mathiak M, Yenisey C, Grant DS, Sharma B, Iozzo RV
(June 1997). “A role for perlecan in the suppression of growth and invasion in fibrosarcoma cells”. Cancer Res. 57 (11): 2130–6. PMID 9187109.
94. ^ Mongiat M, Sweeney SM, San Antonio JD, Fu J, Iozzo RV (February 2003). “Endorepellin,
a novel inhibitor of angiogenesis derived from the C terminus of perlecan”. J. Biol. Chem. 278 (6): 4238–49. doi:10.1074/jbc.M210445200. PMID 12435733. S2CID 21890366.
95. ^ Savorè C, Zhang C, Muir C, Liu R, Wyrwa J, Shu J, Zhau HE,
Chung LW, Carson DD, Farach-Carson MC (2005). “Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding growth factor responses in vitro and tumor growth in vivo”. Clin. Exp. Metastasis. 22 (5): 377–90. doi:10.1007/s10585-005-2339-3.
PMID 16283481. S2CID 25142396.
96. ^ Conde-Knape K (2001). “Heparan sulfate proteoglycans in experimental models of diabetes: a role for perlecan in diabetes complications”. Diabetes Metab. Res. Rev. 17 (6): 412–21. doi:10.1002/dmrr.236.
PMID 11757076. S2CID 24443158.
97. ^ Pillarisetti S (2000). “Lipoprotein modulation of subendothelial heparan sulfate proteoglycans (perlecan) and atherogenicity”. Trends Cardiovasc. Med. 10 (2): 60–5. doi:10.1016/S1050-1738(00)00048-7.
PMID 11150731.
98. ^ Segev A, Nili N, Strauss BH (2004). “The role of perlecan in arterial injury and angiogenesis”. Cardiovasc. Res. 63 (4): 603–10. doi:10.1016/j.cardiores.2004.03.028. PMID 15306215.
99. ^ Wasty F, Alavi MZ, Moore
S (April 1993). “Distribution of glycosaminoglycans in the intima of human aortas: changes in atherosclerosis and diabetes mellitus”. Diabetologia. 36 (4): 316–22. doi:10.1007/BF00400234. PMID 8477876. S2CID 22550300.
100. ^ Vogl-Willis
CA, Edwards IJ (April 2004). “High-glucose-induced structural changes in the heparan sulfate proteoglycan, perlecan, of cultured human aortic endothelial cells”. Biochim. Biophys. Acta. 1672 (1): 36–45. doi:10.1016/j.bbagen.2004.02.005.
PMID 15056491.
101. ^ Tamsma JT, van den Born J, Bruijn JA, Assmann KJ, Weening JJ, Berden JH, Wieslander J, Schrama E, Hermans J, Veerkamp JH (March 1994). “Expression of glomerular extracellular matrix components in human diabetic
nephropathy: decrease of heparan sulphate in the glomerular basement membrane”. Diabetologia. 37 (3): 313–20. doi:10.1007/BF00398060. PMID 8174847. S2CID 21069219.
102. ^ van Det NF, van den Born J, Tamsma JT, Verhagen NA, Berden JH,
Bruijn JA, Daha MR, van der Woude FJ (April 1996). “Effects of high glucose on the production of heparan sulfate proteoglycan by mesangial and epithelial cells”. Kidney Int. 49 (4): 1079–89. doi:10.1038/ki.1996.157. PMID 8691728.
103. ^
Olsson U, Bondjers G, Camejo G (March 1999). “Fatty acids modulate the composition of extracellular matrix in cultured human arterial smooth muscle cells by altering the expression of genes for proteoglycan core proteins”. Diabetes. 48
(3): 616–22. doi:10.2337/diabetes.48.3.616. PMID 10078565.
104. ^ Yamamoto C, Wakata T, Fujiwara Y, Kaji T (February 2005). “Induction of synthesis of a large heparan sulfate proteoglycan, perlecan, by thrombin in cultured human coronary
smooth muscle cells”. Biochim. Biophys. Acta. 1722 (1): 92–102. doi:10.1016/j.bbagen.2004.11.017. PMID 15716125.
105. ^ Shimizu-Hirota R, Sasamura H, Mifune M, Nakaya H, Kuroda M, Hayashi M, Saruta T (December 2001). “Regulation of vascular
proteoglycan synthesis by angiotensin II type 1 and type 2 receptors”. J. Am. Soc. Nephrol. 12 (12): 2609–15. doi:10.1681/ASN.V12122609. PMID 11729229.
106. ^ Hopf M, Göhring W, Mann K, Timpl R (August 2001). “Mapping of binding sites
for nidogens, fibulin-2, fibronectin and heparin to different IG modules of perlecan”. J. Mol. Biol. 311 (3): 529–41. doi:10.1006/jmbi.2001.4878. PMID 11493006.
107. ^ Sasaki T, Göhring W, Pan TC, Chu ML, Timpl R (December 1995). “Binding
of mouse and human fibulin-2 to extracellular matrix ligands”. J. Mol. Biol. 254 (5): 892–9. doi:10.1006/jmbi.1995.0664. PMID 7500359.
108. ^ Mongiat M, Taylor K, Otto J, Aho S, Uitto J, Whitelock JM, Iozzo RV (March 2000). “The protein
core of the proteoglycan perlecan binds specifically to fibroblast growth factor-7”. J. Biol. Chem. 275 (10): 7095–100. doi:10.1074/jbc.275.10.7095. PMID 10702276. S2CID 9078105.
109. ^ Mongiat M, Otto J, Oldershaw R, Ferrer F, Sato
JD, Iozzo RV (March 2001). “Fibroblast growth factor-binding protein is a novel partner for perlecan protein core”. J. Biol. Chem. 276 (13): 10263–71. doi:10.1074/jbc.M011493200. PMID 11148217. S2CID 22631858.
110. ^ Smeland S, Kolset
SO, Lyon M, Norum KR, Blomhoff R (September 1997). “Binding of perlecan to transthyretin in vitro”. Biochem. J. 326 ( Pt 3) (3): 829–36. doi:10.1042/bj3260829. PMC 1218739. PMID 9307034.
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