Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions.
Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions.
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DOI：
10.1172/jci118293
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发表时间：
1995-11
期刊：
影响因子：
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通讯作者：
E. Wilson;K. Sudhir;H. Ives
中科院分区：
文献类型：
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作者：
E. Wilson;K. Sudhir;H. Ives
循环机械应变（1hz）引起新生大鼠血管平滑肌细胞因PDGF的产生和分泌而产生有丝分裂反应。在本研究中，对机械应变的感知机制进行了研究。硅胶弹性体应变板以不同密度涂覆弹性蛋白、层粘连蛋白、I型胶原蛋白、纤维连接蛋白或玻璃体连接蛋白。通过在培养皿下循环应用真空来施加应变。细胞在每种基质蛋白上粘附、扩散和增殖，但对菌株的有丝分裂反应依赖于基质。菌株增加了胶原蛋白、纤维连接蛋白或玻璃体连接蛋白细胞的DNA合成，但没有增加弹性蛋白或层粘连蛋白细胞的DNA合成。当菌株作用于同时含有层粘连蛋白和玻璃体粘连蛋白的基质时，菌株对有丝分裂的反应取决于基质中玻璃体粘连蛋白的含量。可溶性纤维连接蛋白（0-50微克/毫升）和整合素结合肽GRGDTP（100微克/毫升）均可阻断固定胶原上生长的细胞对机械应变的有丝分裂反应。可溶性层粘连蛋白和无活性肽GRGESP均不能阻断对菌株的反应。GRGDTP不改变有丝分裂对外源性PDGF或α -凝血酶的反应，但在应变反应中阻止PDGF的分泌。此外，GRGDTP，而不是GRGESP，阻止了PDGF-A链启动子890 bp氯霉素乙酰转移酶构建物的表达，该构建物被瞬时转染到血管平滑肌细胞中。最后，对菌株的反应被β 3和α v β 5整合素抗体所消除，但不被β 1整合素抗体所消除。因此，整合素和特定基质蛋白之间的相互作用是血管平滑肌细胞感知机械应变的原因。
Cyclic mechanical strain (1 Hz) causes a mitogenic response in neonatal rat vascular smooth muscle cells due to production and secretion of PDGF. In this study, the mechanism for sensing mechanical strain was investigated. Silicone elastomer strain plates were coated at varying densities with elastin, laminin, type I collagen, fibronectin, or vitronectin. Strain was applied by cyclic application of a vacuum under the dishes. Cells adhered, spread, and proliferated on each matrix protein, but the mitogenic response to strain was matrix dependent. Strain increased DNA synthesis in cells on collagen, fibronectin, or vitronectin, but not in cells on elastin or laminin. When strain was applied on matrices containing both laminin and vitronectin, the mitogenic response to strain depended upon the vitronectin content of the matrix. Fibronectin, in soluble form (0-50 micrograms/ml), and the integrin binding peptide GRGDTP (100 micrograms/ml) both blocked the mitogenic response to mechanical strain in cells grown on immobilized collagen. Neither soluble laminin nor the inactive peptide GRGESP blocked the response to strain. GRGDTP did not alter the mitogenic response to exogenous PDGF or alpha-thrombin but did prevent the secretion of PDGF in response to strain. Furthermore, GRGDTP, but not GRGESP, prevented strain-induced expression of a PDGF-A chain promoter 890 bp-chloramphenicol acetyltransferase construct that was transiently transfected into vascular smooth muscle cells. Finally, the response to strain was abrogated by antibodies to both beta 3 and alpha v beta 5 integrins but not by an antibody to beta 1 integrins. Thus interaction between integrins and specific matrix proteins is responsible for sensing mechanical strain in vascular smooth muscle cells.