© 1998 American Heart Association, Inc.
Original Contributions |
Tetraspanin CD9 Is Associated With Very Late–Acting Integrins in Human Vascular Smooth Muscle Cells and Modulates Collagen Matrix Reorganization
From the Laboratoire de Pharmacologie et Physiologie Cellulaires, ERS CNRS 653, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, Illkirch (A.S., A.B.); INSERM U 311, Etablissement de Transfusion Sanguine, Strasbourg (S.M., D.O.A., F.L.); and Laboratoire de Pharmacognosie, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, Illkirch (G.H.-A.), France.
Correspondence to Alain Beretz, Faculté de Pharmacie, BP24, 67401 Illkirch, France. E-mail aberetz{at}pharma.u-strasbg.fr
Abstract—CD9, a member of the
tetraspanin family, and very late–acting (VLA) integrins are known to
associate and form functional units on the surface of several cell
types. We studied the changes in expression of CD9 and
ß1-integrins (CD29, VLA) in human vascular smooth muscle
cells (VSMCs) under in vitro culture conditions mimicking proliferative
vascular diseases. We also investigated possible interactions between
CD9 and VLA integrins in VSMCs. We found that CD9 is highly expressed
in VSMCs and is subject to modulation, depending on the
proliferative/contractile state of the cells. In the contractile
phenotype, the levels of CD9, CD81, another tetraspanin, and
CD29 are 
50% of those found in the proliferative phenotype.
Coimmunoprecipitation experiments showed physical association between
CD9 and CD29. CD9 was mainly associated with 
2 and
3-integrins (CD49b and c) and also with
5-integrin to a weaker extent. Functionally, the
addition of anti-CD9 monoclonal antibodies (MoAbs) doubled the extent
of collagen gel contraction mediated by VSMCs, a model for the
reorganization of the extracellular collagen matrix occurring in the
vessel wall. Anti-CD29 MoAbs inhibited gel contraction, but anti-CD9
MoAbs counteracted this inhibitory effect of anti-CD29
MoAbs. Transfection of human CD9 into Chinese hamster ovary cells more
than doubled the extent of Chinese hamster ovary cell–mediated
collagen gel contraction (130% stimulation), confirming a role for CD9
in extracellular matrix reorganization. Thus, CD9 seems to be involved
in the modulation of VLA integrin–mediated collagen matrix
reorganization by VSMCs. These findings suggest that high CD9
expression is associated with a proliferative state of VSMCs. The role
of CD9 could be to modulate the function of VLA integrins on the
surface of VSMCs.
Key Words: CD9 • tetraspanins • collagen • integrins • smooth muscle
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