Scherberich A, Moog S, Haan-Archipoff G, Azorsa D O, Lanza F, Beretz A
Laboratoire de Pharmacologie et Physiologie Cellulaires, Faculté de Pharmacie, Illkirch France.
Arterioscler Thromb Vasc Biol. 1998 Nov;18(11):1691-7. doi: 10.1161/01.atv.18.11.1691.
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 beta1-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 approximately 50% of those found in the proliferative phenotype. Coimmunoprecipitation experiments showed physical association between CD9 and CD29. CD9 was mainly associated with alpha2 and alpha3-integrins (CD49b and c) and also with alpha5-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.
CD9是四跨膜蛋白家族的成员，已知其与极晚期活化（VLA）整合素相互作用，并在几种细胞类型的表面形成功能单元。我们研究了在模拟增殖性血管疾病的体外培养条件下，人血管平滑肌细胞（VSMC）中CD9和β1整合素（CD29，VLA）表达的变化。我们还研究了VSMC中CD9与VLA整合素之间可能的相互作用。我们发现CD9在VSMC中高表达，并且根据细胞的增殖/收缩状态受到调节。在收缩表型中，CD9、另一种四跨膜蛋白CD81和CD29的水平约为增殖表型中的50%。免疫共沉淀实验表明CD9与CD29之间存在物理关联。CD9主要与α2和α3整合素（CD49b和c）相关，与α5整合素的关联程度较弱。在功能上，添加抗CD9单克隆抗体（MoAb）使VSMC介导的胶原凝胶收缩程度增加了一倍，这是血管壁中发生的细胞外胶原基质重组的模型。抗CD29 MoAb抑制凝胶收缩，但抗CD9 MoAb抵消了抗CD29 MoAb的这种抑制作用。将人CD9转染到中国仓鼠卵巢细胞中，使中国仓鼠卵巢细胞介导的胶原凝胶收缩程度增加了一倍多（刺激130%），证实了CD9在细胞外基质重组中的作用。因此，CD9似乎参与了VLA整合素介导的VSMC胶原基质重组的调节。这些发现表明CD9高表达与VSMC的增殖状态相关。CD9的作用可能是调节VSMC表面VLA整合素的功能。
