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Thrombospondin mediates migration and potentiates platelet-derived growth factor-dependent migration of calf pulmonary artery smooth muscle cells

dc.contributor.authorYabkowitz, Rachelen_US
dc.contributor.authorMansfield, Pamela J.en_US
dc.contributor.authorRyan, Una S.en_US
dc.contributor.authorSuchard, Suzanne J.en_US
dc.date.accessioned2007-04-06T18:04:49Z
dc.date.available2007-04-06T18:04:49Z
dc.date.issued1993-10en_US
dc.identifier.citationYabkowitz, Rachel; Mansfield, Pamela J.; Ryan, Una S.; Suchard, Suzanne J. (1993)."Thrombospondin mediates migration and potentiates platelet-derived growth factor-dependent migration of calf pulmonary artery smooth muscle cells." Journal of Cellular Physiology 157(1): 24-32. <http://hdl.handle.net/2027.42/49886>en_US
dc.identifier.issn0021-9541en_US
dc.identifier.issn1097-4652en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/49886
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=8408239&dopt=citationen_US
dc.description.abstractA precipitating factor in the development of atherosclerotic lesions is the inappropriate migration and proliferation of vascular smooth muscle cells (SMC) within the intima of the vessel wall. Focusing on the role of extracellular matrix proteins in SMC migration, we have demonstrated that thrombospondin (TSP) itself is a potent modulator of SMC motility and acts to potentiate platelet-derived growth factor (PDGF)-mediated SMC migration as well. Migration of SMC to TSP was dose dependent. Interestingly, maximal SMC migration to TSP exceeded that to either PDGF or basic fibroblast growth factor (bFGF). The distal COOH terminus of TSP was shown to mediate SMC migration as demonstrated by complete inhibition of the response by monoclonal antibody (mAb) C6.7. Nevertheless, proteolytic fragments of TSP were not as potent as intact TSP in mediating SMC migration. Only by combining the heparin-binding domain (HBD) with the 140 kD COOH terminal fragment was SMC migration restored to levels seen with intact TSP. Based on antibody inhibition studies, an Α v -containing integrin receptor, but not Α v Β 1 or Α v Β 3 , appeared to be involved in SMC migration to TSP. The coincidental expression of PDGF and TSP at sites of vascular injury and inflammation led us to evaluate the effect of suboptimal levels of TSP on SMC responsiveness to PDGF. SMC migration in response to PDGF was enhanced nearly 60% in the presence of suboptimal concentrations of TSP. This effect was specific for PDGF and dependent on the concentration of TSP with maximal potentiation obtained between 50–100 nM TSP, concentrations tenfold lower than those necessary for SMC migration to TSP itself. mAb C6.7 completely inhibited enhancement but, as with SMC migration to TSP alone, TSP proteolytic fragments did not possess the effectiveness of the intact molecule. Additional experiments assessing SMC migration to PDGF demonstrated that PDGF stimulated SMC motility indirectly by inducing TSP synthesis. These studies suggested that TSP functions as an autocrine motility factor to modulate SMC migration, which in conjunction with PDGF could serve to aggravate and accelerate development of atherosclerotic lesions at sites of vascular injury or inflammation. © 1993 Wiley-Liss, Inc.en_US
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dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherLife and Medical Sciencesen_US
dc.subject.otherCell & Developmental Biologyen_US
dc.titleThrombospondin mediates migration and potentiates platelet-derived growth factor-dependent migration of calf pulmonary artery smooth muscle cellsen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbsecondlevelKinesiology and Sportsen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor Michigan 48109 ; Amgen, Inc., Amgen Center, 1840 DeHavilland Dr., Thousand Oaks, California 91320-1789en_US
dc.contributor.affiliationumDepartment of Pediatrics, University of Michigan School of Medicine, Ann Arbor Michigan 48109en_US
dc.contributor.affiliationumDepartment of Pediatrics, University of Michigan School of Medicine, Ann Arbor Michigan 48109en_US
dc.contributor.affiliationotherDepartment of Surgery, Washington University, St. Louis, Missouri 63110en_US
dc.identifier.pmid8408239en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/49886/1/1041570104_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/jcp.1041570104en_US
dc.identifier.sourceJournal of Cellular Physiologyen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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