ライフサイエンスコーパス: perlecan

1 extracellular matrix (via laminin, agrin, or perlecan).

2 s collagenic tail (ColQ) to the proteoglycan perlecan.

3 an sulfate proteoglycans (HSPGs), especially perlecan.

4 ot to basement membranes containing the HSPG perlecan.

5 4(V)-NTD-binding proteins are glypican-1 and perlecan.

6 nd phosphorylation of FAK and Akt of SMCs on perlecan.

7 lar matrices, with a distribution similar to perlecan.

8 or significantly reduced levels of wild-type perlecan.

9 ted in reduced amounts of nearly full-length perlecan.

10 teins that interact with the protein core of perlecan.

11 lanogaster homolog of the vertebrate protein Perlecan.

12 membrane including laminin-5, entactin, and perlecan.

13 an antisense vector targeting domain III of perlecan.

14 showed a decrease in the HSPG core protein, perlecan.

15 r roles as cell surface attachment sites for perlecan.

16 ies secreted into the media were decorin and perlecan.

17 ributed to the heparan sulfate GAG chains of perlecan.

18 ts with the glycosaminoglycan side chains of perlecan.

19 ellular matrix heparan sulfate proteoglycan, perlecan.

20 a skeletal disease resulting from decreased perlecan.

21 Perlecan (10 microg/ml) evoked unreportedly high, in vit

22 ersican (3.2-fold), biglycan (2.0-fold), and perlecan (2.0-fold), whereas decorin mRNA levels decreas

23 ranscripts, which encode the core protein of perlecan, a basement membrane proteoglycan.

24 secreted heparan sulfate proteoglycan (HSPG) perlecan, a component of the extracellular matrix.

25 Perlecan, a heparan sulfate proteoglycan of basement mem

26 Perlecan, a heparan sulfate proteoglycan, has been sugge

27 Perlecan, a HSPG normally confined to the mesangium in m

28 Perlecan, a large heparan sulfate proteoglycan, is a com

29 Perlecan, a large, multi-domain, heparan sulfate proteog

30 We now studied perlecan, a major cell surface HSPG genetically distinct

31 In an in vivo search of novel partners for perlecan, a major heparan sulfate proteoglycan of baseme

32 his study was to discover novel partners for perlecan, a major heparan sulfate proteoglycan of baseme

33 Here we show that perlecan, a multifunctional heparan sulfate proteoglycan

34 Perlecan, a ubiquitous basement membrane heparan sulfate

35 Perlecan, a ubiquitous heparan sulfate proteoglycan, pos

36 Perlecan, a widespread heparan sulfate proteoglycan, fun

37 ondrocytes had intracellular accumulation of perlecan, an extracellular matrix protein, but not of ty

38 use et al. demonstrate that dystroglycan and perlecan, an extracellular matrix receptor and its ligan

39 be considered a novel biological ligand for perlecan, an interaction that could influence cancer gro

40 These results indicate that perlecan and aggrecan would be the principal candidate p

41 of 200 kDa and larger and were identified as perlecan and aggrecan.

42 study shows that collagen XVIII is, next to perlecan and agrin, the third basal lamina heparan sulfa

43 oimmunoprecipitated with an antibody against perlecan and bound in solution to recombinant domain III

44 Perlecan and ECM1 were also co-expressed by a variety of

45 Here, we show that both perlecan and endorepellin bind directly and with high af

46 is, levels of the basement membrane proteins perlecan and fibronectin were severalfold higher than in

47 chanical strain stimulated the production of perlecan and heparan sulfate glycosaminoglycans by endot

48 n surface glia, AdamTS-A acts in parallel to perlecan and in opposition to viking/collagen IV and bet

49 xperiments to investigate the involvement of perlecan and its C-terminal domain V/endorepellin in zeb

50 her basement membrane components) as well as perlecan and laminin isoforms.

51 Collagen IV, pan-laminin, perlecan and laminin-alpha5 in the islet BM were signifi

52 Finally, we examined cooperation between perlecan and low density lipoprotein receptors and found

53 that trol encodes the Drosophila homolog of Perlecan and regulates neuroblast division by modulating

54 nized mesenchyme, with reduced expression of perlecan and semaphorin 3C, and exhibited disorganized F

55 ns between Trol and Hh and between mammalian Perlecan and Shh that are not competed with heparin sulf

56 cells revealed that the HSPG increase was in perlecan and that apoE also stimulated perlecan mRNA exp

57 te-decorated extracellular biomolecule named perlecan and the research relating to its potential as a

58 pericellular coats of HA selectively reduced perlecan and versican turnover, whereas other proteoglyc

59 propose delivery and application schemes for perlecan and/or its domains in bone-regenerative procedu

60 extracellular matrix glycoproteins laminin, perlecan, and agrin mediate the binding to heparin and t

61 aminin-1, nidogen-1, collagens IV and XVIII, perlecan, and agrin.

62 onnexin 43, type IV collagen, laminin-5, and perlecan, and apoptosis was determined by TUNEL or cell-

63 e-2 and increased the synthesis of versican, perlecan, and decorin/biglycan.

64 Versican, biglycan, perlecan, and hyaluronan were present with varying indiv

65 x (ECM) molecules such as Laminin, agrin and perlecan, and plays a role in linking the ECM to the act

66 on between the heparan sulfate proteoglycan, perlecan, and PTEN in the regulation of vascular smooth

67 r, including uvomorulin, integrin alpha8 and perlecan, and suggest that WTI may activate the IGF-II g

68 f syndecan-1, syndecan-4, glypican, decorin, perlecan, and versican.

69 bation with either anti-endorepellin or anti-perlecan antibodies.

70 An anti-perlecan antibody completely abrogated the antiprolifera

71 nstrate that cell-surface syndecan-1 and ECM perlecan are degradative targets of HPSE-1, and syndecan

72 Nidogen and perlecan are large multifunctional basement membrane (BM

73 inin 10, collagen IV, and nidogen-2 (but not perlecan) are considerably lower (<60%) than the average

74 cellular matrix, such as laminin, agrin, and perlecan, are not abundant in brain except in the periva

75 We identify the dystroglycan-ligand perlecan as a novel nodal component and show that dystro

76 kbone and GAG sulfate content, and implicate perlecan as an important macromolecule that is likely in

77 he yeast two-hybrid system and domain III of perlecan as bait, we screened approximately 0.5 10(6) cD

78 s required for the selective accumulation of perlecan at nodes.

79 us controls that produce abundant amounts of perlecan at this developmental time point.

80 Perlecan augments the reduction in phospho-focal adhesio

81 ing perlecan to mutant motor neurons rescues perlecan axon guidance defects.

82 1 and serum induced substantial increases in perlecan bearing chondroitin sulfate and/or heparan sulf

83 The levels of perlecan bearing chondroitin sulfate chains were elevate

84 r extended periods in culture, the amount of perlecan bearing heparan sulfate chains was unaffected b

85 proteins studied, the effects are unique to perlecan, because plating of SMCs on several other basem

86 cell-surface and matrix proteoglycans (e.g., perlecan, biglycan, and syndecans 1 and 3) and mitogenes

87 Because both decorin and perlecan bind growth factors and are proposed to modulat

88 dentified, activity of nidogen overlaps with perlecan binding and accounts for the unusually high deg

89 Perlecan binds the clustering molecule gliomedin and enh

90 Endorepellin (the C-terminal domain V of perlecan) binds the alpha2beta1 integrin on endothelial

91 Cells expressing perlecan but no other proteoglycans bound, internalized,

92 iogenic heparan sulfate proteoglycan (HSPG), perlecan, but not other HSPGs, is dramatically down-regu

93 ulfate and to BM components like laminin and perlecan, but the functional role of these interactions

94 ts stained poorly with antibody specific for perlecan, but there was staining of intracellular inclus

95 The perlecan c-terminal fragment LG3 is generated at increas

96 x composed of large glycoproteins, including perlecan, collagens, and laminins.

97 f the specific heparan sulfate proteoglycan, perlecan, colocalized to islet amyloid deposits, similar

98 Therefore, the dystroglycan-perlecan complex serves as a cell surface acceptor for A

99 Perlecan contained 25% heparan sulfate and 75% chondroit

100 t other products (e.g., apolipoprotein E and perlecan) contained within islet amyloid may be necessar

101 y connected in a spot-welding-like manner by perlecan-containing aggregates.

102 After removal of perlecan-containing suprastructures or after enzyme dige

103 train also increased versican, biglycan, and perlecan core proteins, with a concomitant decrease in d

104 helial cells prevented occlusive thrombosis, perlecan-deficient cells were completely ineffective.

105 tly reconstitutes FGF7 mitogenic activity in perlecan-deficient cells.

106 y reconstituted the activity of FGF-7 in the perlecan-deficient cells.

107 Perlecan-deficient mice did not display demyelination ev

108 ization of myelinating Schwann cells because perlecan-deficient mice had shorter internodes, more num

109 ased PTEN activity was detected in aortas of perlecan-deficient mouse embryos, consistent with SMC hy

110 rotein receptor-related protein did not slow perlecan-dependent internalization.

111 ased PTEN activity associated with increased perlecan deposition and decreased SMC replication rates.

112 D fibroblasts, and augmented fibronectin and perlecan deposition in all three groups.

113 cult to dissect in placental animals because perlecan disruption is embryonic lethal.

114 drying and loaded with plasmid DNA encoding perlecan domain I and VEGF189 and analyzed in vivo for t

115 The plasmid DNA encoding perlecan domain I and VEGF189 loaded scaffolds promoted

116 containing plasmid DNA encoding VEGF189 and perlecan domain I have the potential to induce angiogene

117 Perlecan Domain V (DV) promotes brain angiogenesis by in

118 mployed the yeast two-hybrid system and used perlecan domain V as bait to screen a human keratinocyte

119 The interaction of progranulin with perlecan domain V involved the first two laminin- and ep

120 These results suggest that perlecan domain V represents a promising approach for st

121 r-like modules flanking the LG2 subdomain of perlecan domain V.

122 rn blot analysis revealed elevated levels of perlecan domain V.

123 likely the heparan sulfate chain present on perlecan domain V.

124 y occurring extracellular matrix fragment of perlecan, domain V, which we found had neuroprotective p

125 l insight into the role of the ECM component Perlecan during Drosophila hematopoiesis.

126 Exogenous perlecan effectively reconstituted the activity of FGF-7

127 to perlecan protein core and that exogenous perlecan efficiently reconstitutes FGF7 mitogenic activi

128 fibronectin, serum-stimulated SMCs plated on perlecan exhibited increased PTEN activity, decreased FA

129 helial cells, blocked the down-regulation of perlecan expression and antiproliferative activity of cl

130 Down-regulation of perlecan expression by cleaved and latent antithrombins

131 In this report we blocked perlecan expression by using either constitutive CMV-dri

132 Mechanical regulation of perlecan expression in endothelial cells was governed by

133 growth factor-beta 1, a potent stimulator of perlecan expression in endothelial cells, blocked the do

134 The importance of perlecan expression levels in mediating the antiprolifer

135 Down-regulation of perlecan expression suppresses the invasive behavior of

136 ecause other growth modulators also regulate perlecan expression, this may be a key pathway in the re

137 ir effects is through the down-regulation of perlecan expression.

138 n correlated with their ability to stimulate perlecan expression.

139 DGF-BB, whereas both PDGF isoforms decreased perlecan expression.

140 illin-1) or in combination with fibronectin (perlecan, fibulin-2), in the absence of feeder cells.

141 lular matrix proteins, including nidogen and perlecan (Figure 1, bottom).

142 Altogether, our data shed light on perlecan function by revealing critical roles in Schwann

143 Perlecan functions as a ligand reservoir for various gro

144 These data indicate that perlecan functions as an endogenously produced inhibitor

145 Mutations in the perlecan gene (HSPG2) cause two classes of skeletal diso

146 Mice lacking the perlecan gene (Hspg2) have a severe chondrodysplasia wit

147 we investigated the activity of IFN-gamma on perlecan gene expression and cell growth in colon carcin

148 was markedly attenuated upon obliteration of perlecan gene expression and these effects correlated wi

149 broblast growth factor (bFGF) signaling, and perlecan gene expression in bFGF-stimulated human umbili

150 at IFN-gamma rapidly and efficiently blocked perlecan gene expression with concurrent growth suppress

151 The transcriptional repression of the perlecan gene required intact Stat1 protein, and these e

152 his increased LG3 is the result of increased perlecan generation and cellular release, increased prot

153 anulin, the subdomains interacting most with perlecan harbored granulins F and B.

154 rils and glycosaminoglycans, suggesting that perlecan has an important role in matrix structure.

155 These findings suggest that perlecan has an important role in neuromuscular function

156 Endorepellin, the C-terminal module of perlecan, has angiostatic activity.

157 ad a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chain

158 lin to perlecan was similarly observed using perlecan heparan sulfate glycosaminoglycans (GAGs), and

159 d the FGF10-FGFR2b complex bound to purified perlecan HS and could be released by heparanase.

160 results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK si

161 degrades HS chains of purified syndecan-1 or perlecan HS.

162 in DM appears to be due to decreased hepatic perlecan HSPG.

163 We have disrupted the gene encoding perlecan (Hspg2) in mice.

164 s (GPCs), the basement membrane proteoglycan perlecan (HSPG2), and agrin.

165 lar to the fibronectin binding Ig domains of Perlecan/HSPG2.

166 Perlecan IG3 belongs to the I-set of the IG superfamily

167 t 2.0 A resolution of the mouse nidogen-1 G2-perlecan IG3 complex.

168 the third immunoglobulin (IG)-like domain in perlecan, IG3.

169 soluble FGF-7 specifically bound immobilized perlecan in a heparan sulfate-independent manner.

170 uding the genes for collagen 2, aggrecan and perlecan in both notochord cells and surrounding chondro

171 ur findings demonstrate the critical role of perlecan in cartilage development.

172 ant site and that cleave LG3 from endogenous perlecan in cultured mouse and human cells.

173 e of the heparan sulfate proteoglycan (HSPG) perlecan in islet amyloid deposits, suggesting a role fo

174 ohistochemistry revealed reduced staining of perlecan in kidney from apoE-null mice.

175 The previously established key role of perlecan in mediating bFGF stimulation of endothelial ce

176 zed sarcomeres, suggesting an involvement of perlecan in myopathies.

177 that SMC adhesion to basement membranes, and perlecan in particular, up-regulate the expression of fo

178 e SJS mutations result in different forms of perlecan in reduced levels that are secreted to the extr

179 nd degradation of fibrin(ogen), nidogen, and perlecan in the adventitia of descending aortas.

180 is not required for the deposition of UNC-52/perlecan in the basal lamina, nor for the initiation of

181 ranase, an endoglycosidase, colocalized with perlecan in the basement membrane and in epithelial clef

182 robe for HS in SMGs, and it colocalized with perlecan in the basement membrane and partly colocalized

183 We revealed a role for perlecan in the longitudinal elongation and organization

184 alyses revealed colocalization of FGF-BP and perlecan in the pericellular stroma of various squamous

185 model of SJS to determine whether a role for perlecan in these functions could account for PNH when p

186 mutations that resulted in various forms of perlecan in three unrelated patients with SJS.

187 ession of constitutively active Akt reversed perlecan-induced SMC growth arrest while morpholino anti

188 growth and increased PTEN activity mediates perlecan-induced suppression of SMC proliferation.

189 reduction in cell spreading, we report that perlecan-induced up-regulation of FRNK is independent of

190 l domain of the heparan sulfate proteoglycan perlecan, inhibits angiogenesis by simultaneously bindin

191 the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the alpha2beta1-inte

192 l domain of the heparan sulfate proteoglycan perlecan, inhibits several aspects of angiogenesis.

193 inin-5, type IV collagen, type VII collagen, perlecan, integrin alpha6, and epithelial cell different

194 Thus, progranulin/perlecan interaction could contribute to a fine regulati

195 lts uncover incorporation of Collagen IV and Perlecan into BMs as a major determinant of organ shape

196 e and process the extracellular proteoglycan perlecan into fragments containing the endorepellin C-te

197 Perlecan is a large heparan sulfate (HS) proteoglycan pr

198 Perlecan is a multifaceted heparan sulfate proteoglycan

199 Thus, perlecan is a potent inducer of tumor growth and angioge

200 Our previous studies showed perlecan is a potent inhibitor of serum-stimulated SMC g

201 Thus, these data show that perlecan is a potent inhibitor of SMC proliferation and

202 Up-regulation of FRNK by perlecan is actively and continuously regulated.

203 Perlecan is discussed as a potential biological adjunct

204 These findings indicate that perlecan is essential for the integrity of somitic muscl

205 neurons during OGD and de novo synthesis of perlecan is increased during reperfusion, even 24 h afte

206 n these functions could account for PNH when perlecan is lacking.

207 d, whereas the corresponding binding site on perlecan is more variable.

208 Perlecan is present in a variety of basement membranes a

209 Because perlecan is present in both endothelial and smooth muscl

210 Therefore, perlecan is required for Sema-1a-PlexA-mediated repulsiv

211 Perlecan is the major HSPG of mesangial matrix and suben

212 Endorepellin, the C-terminal domain of perlecan, is a powerful angiogenesis inhibitor.

213 Endorepellin, the C-terminal domain of perlecan, is an angiostatic molecule that acts as a pote

214 Conversely, another HSPG, perlecan, is an important component of basement membrane

215 Perlecan knock-in mice were developed to model Schwartz-

216 The extracellular proteoglycan UNC-52/Perlecan linked the dense body to the hemidesmosome on t

217 glycan or in its extracellular matrix ligand Perlecan lose polarity under energetic stress.

218 We found that pre-synthesized perlecan may be exocytosed by neurons during OGD and de

219 nd to examine new interactions through which perlecan may influence cell behavior.

220 gamma-mediated transcriptional repression of perlecan may represent a novel antitumoral effect of thi

221 Our results demonstrate that perlecan mediates internalization and lysosomal delivery

222 eritracheal distributions of collagen IV and Perlecan, misregulated ASP growth, and abrogated develop

223 The perlecan molecule, with its heparan sulfate glycosylatio

224 The perlecan morphants show a severe myopathy characterized

225 In the perlecan morphants, primary intersegmental vessel sprout

226 as in perlecan and that apoE also stimulated perlecan mRNA expression by >2-fold.

227 gation, the spatial and temporal patterns of perlecan mRNA expression in the mouse embryo during the

228 Sema-1a- and PlexA-null mutant embryos, and perlecan mutants genetically interact with PlexA and Sem

229 Motor axon guidance defects in perlecan mutants resemble those observed in Sema-1a- and

230 Endorepellin, the C-terminal module of perlecan, negatively regulates angiogenesis counter to i

231 t DM, type IV collagen alpha1-alpha6 chains, perlecan, nidogen-1, nidogen-2, and netrin-4 were found

232 Starved Dystroglycan or Perlecan null cells activate AMPK normally, but do not a

233 s (EC) release LG3, a C-terminal fragment of perlecan of potential importance in vascular remodeling

234 The differential regulation by perlecan of these different aspects of vascular repair m

235 dies suggest that the enhancement effects of perlecan on amylin fibril formation are mediated primari

236 n, fibronectin, collagen type IV, agrin, and perlecan-on adhesion and TEER was assessed using an elec

237 partially rescued by microinjection of human perlecan or endorepellin.

238 LG3 from previous extracellularly deposited perlecan) or both.

239 Collagen IV and perlecan originate predominantly from the lens epitheliu

240 ting that the heparan sulfate side chains of perlecan play a biologically important role in negativel

241 Similarly, perlecan plays an important role in chondrogenesis and s

242 embrane heparan sulfate proteoglycan (HSPG), perlecan (Pln), mRNA, and protein has been examined duri

243 mooth muscle cell (SMC) replication and that perlecan (PN), a basement membrane heparan sulfate prote

244 In vitro experiments with perlecan-positive rat mesangial cells showed that FGF2-i

245 fragment of the heparan sulfate proteoglycan perlecan, possesses angiostatic activity via dual recept

246 l domain of the heparan sulfate proteoglycan perlecan, possesses angiostatic activity.

247 We discovered that the C terminus of perlecan potently inhibited four aspects of angiogenesis

248 LG domains of non-neural (muscle) agrin and perlecan promote AChR clustering in the presence of lami

249 t fibroblast growth factor-7 (FGF7) binds to perlecan protein core and that exogenous perlecan effici

250 Thus, perlecan protein core should be considered a novel biolo

251 ogical axis that links a soluble fragment of perlecan protein core to the major cell surface receptor

252 of FGF7 to various domains and subdomains of perlecan protein core.

253 Perlecan protein is found in both the CNS and the periph

254 In the present study, perlecan purified from the Engelbreth-Holm-Swarm (EHS) t

255 mply that transcriptional changes leading to perlecan reduction may represent the disease mechanism f

256 space, and consistent with this, blockade of perlecan reversed the antiproliferative effect of apoE.

257 Perlecan's developmental functions are difficult to diss

258 th-Holm-Swarm (EHS) tumor was used to define perlecan's interactions with amylin (i.e., islet amyloid

259 alized to islet amyloid deposits, similar to perlecan's known involvement with other amyloid proteins

260 hanges in C1532Yneo mice, leading to reduced perlecan secretion and a skeletal disease phenotype char

261 s indicate that matrix proteoglycans such as perlecan serve as functional docking platforms for FGF2

262 Thus, Perlecan signaling through Dystroglycan may determine wh

263 Perlecan staining is weak in intermediate lesions but st

264 Perlecan supports SMC adhesion, although there is reduce

265 ced by highly invasive mouse melanoma cells, perlecan suppression caused substantial inhibition of tu

266 asia, however, was abrogated only in part by perlecan suppression.

267 ransfected cells produced significantly less perlecan than parent cells and showed a reduced ability

268 unc-52 encodes homologs of mammalian perlecan that are located extracellularly between muscle

269 patients with SJS either produced truncated perlecan that lacked domain V or significantly reduced l

270 which are also found in laminin, agrin, and perlecan, that are dystroglycan ligands.

271 ent membrane proteins, homologs of mammalian perlecan, that are important for body wall muscle assemb

272 PNH that is due to hypomorphic mutations of perlecan, the major proteoglycan of basement membranes.

273 PAT-4/ILK requires the ECM component UNC-52/perlecan, the transmembrane protein integrin, and the no

274 We have previously shown perlecan to be selectively up-regulated in the glomeruli

275 It also requires conjugation of the agrin or perlecan to laminin together with laminin polymerization

276 Restoring perlecan to mutant motor neurons rescues perlecan axon g

277 There is deficiency of heparan sulfate and perlecan, together with accumulation of collagens, in th

278 The C terminus of perlecan was active at nanomolar concentrations and bloc

279 The core protein of perlecan was an exclusive component of this network wher

280 By several criteria, catabolism via perlecan was distinct from either coated pits or the syn

281 ith an antisense vector we demonstrated that perlecan was essential to the strain-mediated effects on

282 and electron microscopy methodology, intact perlecan was found to enhance amylin fibril formation in

283 The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and pl

284 Internalization via perlecan was inhibited by genistein but unaffected by cy

285 Perlecan was linked to either chondroitin sulfate, hepar

286 Biochemically, truncated perlecan was not secreted by the patient fibroblasts, bu

287 n of the matrix heparan sulfate proteoglycan perlecan was observed, along with massive accumulation o

288 Growth inhibition by perlecan was rescued by overexpressing a constitutively

289 The binding of human amylin to perlecan was similarly observed using perlecan heparan s

290 finity to the heparan sulfate side chains of perlecan, we investigated the activity of IFN-gamma on p

291 The heparan sulfate chains on growth plate perlecan were considerably smaller than the chondroitin

292 (found in both layers of the duplex BM) and perlecan were lost entirely, with no restoration evident

293 otein E and the heparan sulfate proteoglycan perlecan, which are typically observed in other forms of

294 tering at the postsynaptic membrane requires perlecan, which binds both AChE and dystroglycan.

295 ting cells and second through recruitment of Perlecan, which counters constriction by Collagen IV.

296 me binds to the heparan-sulfate proteoglycan perlecan, which in turn binds to the dystroglycan comple

297 tissue stiffness and oppose the function of perlecan, which reduces tissue stiffness.

298 n, but not rat amylin, bound immobilized EHS perlecan with a single dissociation constant (Kd) = 2.75

299 By inhibiting the expression of perlecan with an antisense vector we demonstrated that p

300 1, produce the heparan sulfate proteoglycan, perlecan, with a molecular mass of 640 kDa as well as sm