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Perlecan inhibits smooth muscle cell adhesion to fibronectin : Role of heparan sulfate

Lundmark, Karin LU ; Tran, Phan Kiet LU ; Kinsella, Michael G. ; Clowes, Alexander W. ; Wight, Thomas N. and Hedin, Ulf (2001) In Journal of Cellular Physiology 188(1). p.67-74
Abstract


Smooth muscle cell migration, proliferation, and deposition of extracellular matrix are key events in atherogenesis and restenosis development. To explore the mechanisms that regulate smooth muscle cell function, we have investigated whether perlecan, a basement membrane heparan sulfate proteoglycan, modulates interaction between smooth muscle cells and other matrix components. A combined substrate of fibronectin and perlecan showed a reduced adhesion of rat aortic smooth muscle cells by 70-90% in comparison to fibronectin alone. In contrast, perlecan did not interfere with cell adhesion to laminin. Heparinase treated perlecan lost 60% of its anti-adhesive effect. Furthermore, heparan sulfate as well as... (More)


Smooth muscle cell migration, proliferation, and deposition of extracellular matrix are key events in atherogenesis and restenosis development. To explore the mechanisms that regulate smooth muscle cell function, we have investigated whether perlecan, a basement membrane heparan sulfate proteoglycan, modulates interaction between smooth muscle cells and other matrix components. A combined substrate of fibronectin and perlecan showed a reduced adhesion of rat aortic smooth muscle cells by 70-90% in comparison to fibronectin alone. In contrast, perlecan did not interfere with cell adhesion to laminin. Heparinase treated perlecan lost 60% of its anti-adhesive effect. Furthermore, heparan sulfate as well as heparin reduced smooth muscle cell adhesion when combined with fibronectin whereas neither hyaluronan nor chondroitin sulfate had any anti-adhesive effects. Addition of heparin as a second coating to a preformed fibronectin matrix did not affect cell adhesion. Cell adhesion to the 105- and 120 kDa cell-binding fragments of fibronectin, lacking the main heparin-binding domains, was also inhibited by heparin. In addition, co-coating of fibronectin and
3
H-heparin showed that heparin was not even incorporated in the substrate. Morphologically, smooth muscle cells adhering to a substrate prepared by co-coating of fibronectin and perlecan or heparin were small, rounded, lacked focal contacts, and showed poorly developed stress fibers of actin. The results show that the heparan sulfate chains of perlecan lead to altered interactions between smooth muscle cells and fibronectin, possibly due to conformational changes in the fibronectin molecule. Such interactions may influence smooth muscle cell function in atherogenesis and vascular repair processes.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cellular Physiology
volume
188
issue
1
pages
67 - 74
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:11382923
  • scopus:0035008832
ISSN
0021-9541
DOI
10.1002/jcp.1094
language
English
LU publication?
no
id
35586294-1a4c-4366-8d9b-8d2d6e4f6097
date added to LUP
2019-07-01 22:54:21
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2024-09-18 06:11:55
@article{35586294-1a4c-4366-8d9b-8d2d6e4f6097,
  abstract     = {{<p><br>
                            Smooth muscle cell migration, proliferation, and deposition of extracellular matrix are key events in atherogenesis and restenosis development. To explore the mechanisms that regulate smooth muscle cell function, we have investigated whether perlecan, a basement membrane heparan sulfate proteoglycan, modulates interaction between smooth muscle cells and other matrix components. A combined substrate of fibronectin and perlecan showed a reduced adhesion of rat aortic smooth muscle cells by 70-90% in comparison to fibronectin alone. In contrast, perlecan did not interfere with cell adhesion to laminin. Heparinase treated perlecan lost 60% of its anti-adhesive effect. Furthermore, heparan sulfate as well as heparin reduced smooth muscle cell adhesion when combined with fibronectin whereas neither hyaluronan nor chondroitin sulfate had any anti-adhesive effects. Addition of heparin as a second coating to a preformed fibronectin matrix did not affect cell adhesion. Cell adhesion to the 105- and 120 kDa cell-binding fragments of fibronectin, lacking the main heparin-binding domains, was also inhibited by heparin. In addition, co-coating of fibronectin and <br>
                            <sup>3</sup><br>
                            H-heparin showed that heparin was not even incorporated in the substrate. Morphologically, smooth muscle cells adhering to a substrate prepared by co-coating of fibronectin and perlecan or heparin were small, rounded, lacked focal contacts, and showed poorly developed stress fibers of actin. The results show that the heparan sulfate chains of perlecan lead to altered interactions between smooth muscle cells and fibronectin, possibly due to conformational changes in the fibronectin molecule. Such interactions may influence smooth muscle cell function in atherogenesis and vascular repair processes.</p>}},
  author       = {{Lundmark, Karin and Tran, Phan Kiet and Kinsella, Michael G. and Clowes, Alexander W. and Wight, Thomas N. and Hedin, Ulf}},
  issn         = {{0021-9541}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{67--74}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Cellular Physiology}},
  title        = {{Perlecan inhibits smooth muscle cell adhesion to fibronectin : Role of heparan sulfate}},
  url          = {{http://dx.doi.org/10.1002/jcp.1094}},
  doi          = {{10.1002/jcp.1094}},
  volume       = {{188}},
  year         = {{2001}},
}