Mechanical Strain Induces Growth of Vascular Smooth Muscle Cells via Autocrine Action of PDGF

• Published in: The Journal of cell biology 1993-11, Vol.123 (3), p.741-747
• Main Authors: Wilson, Emily, Mai, Qing, Sudhir, Krishnankutty, Weiss, Robert H., Ives, Harlan E.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Antibodies; Becaplermin; Biological and medical sciences; Cell culture techniques; Cell Division - drug effects; Cell growth; Cell Line; Cells; Cellular biology; Culture Media, Conditioned; Cultured cells; DNA; DNA - biosynthesis; Endothelial cells; Fundamental and applied biological sciences. Psychology; Humans; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscular system; Physical growth; Platelet-Derived Growth Factor - biosynthesis; Platelet-Derived Growth Factor - pharmacology; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-sis; Rats; Recombinant Proteins - pharmacology; RNA, Messenger - metabolism; Rodents; Smooth muscle myocytes; Sprains and strains; Stress, Mechanical; Striated muscle. Tendons; Structural strain; Thrombin - pharmacology; Thymidine - metabolism; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.123.3.741

The effect of cyclic mechanical strain on growth of neonatal rat vascular smooth muscle (VSM) cells were examined. Cells were grown on silicone elastomer plates subjected to cyclic strain (60 cycle/min) by application of a vacuum under the plates. A 48 h exposure to mechanical strain increased the basal rate of thymidine incorporation by threefold and increased cell number by 40% compared with cells grown on stationary rubber plates. Strain also increased the rate of thymidine incorporation in response to α-thrombin (from 15- to 33-fold), but not to PDGF. As determined by thymidine autoradiography, strain alone induced a fourfold increase in labeled nuclei at the periphery of dishes, where strain is maximal, and a 2-3-fold increase at the center of dishes. Strain appeared to induce the production of an autocrine growth factor(s), since conditioned medium from cells subjected to strain induced a fourfold increase in DNA synthesis in control cells. Western blots of medium conditioned on the cells subjected to strain indicate that the cells secrete both AA and BB forms of PDGF in response to strain. Northern blots of total cell RNA from cells exposed to strain for 24 h show increased steady-state level of mRNA for PDGF-A. Lastly, polyclonal antibodies to the AA form of PDGF reduced by 75% the mitogenic effect of strain and polyclonal antibodies to AB-PDGF reduced mitogenicity by 50%. Antibodies to bFGF did not significantly reduce the strain-induced thymidine incorporation. Thus, the mechanism of strain-induced growth appears to involve the intermediary action of secreted PDGF.