Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions.
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.
Wilson
E
E
Division of Nephrology, University of California, San Francisco 94143, USA.
Sudhir
K
K
Ives
H E
HE
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D004261:DNA Replication; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D015870:Gene Expression; D016023:Integrins / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D013314:Stress, Mechanical
D016326:Extracellular Matrix Proteins; D016023:Integrins; D010982:Platelet-Derived Growth Factor