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(Hypertension. 1997;29:356.)
© 1997 American Heart Association, Inc.

Arthur C. Corcoran Memorial Lecture

-Thrombin Stimulates sis-Inducing Factor-A DNA Binding Activity in Rat Aortic Smooth Muscle Cells

G. Jayarama Bhat; S. Thomas Abraham; Harold A. Singer; Kenneth M. Baker

From the Weis Center for Research, Geisinger Clinic, Danville, Pa.

Correspondence to G. Jayarama Bhat, PhD, Weis Center for Research, 100 N Academy Ave, Danville, PA 17822

Exposure of rat aortic vascular smooth muscle cells to -thrombin resulted in the appearance of sis-inducing factor-A (SIF-A)-like DNA binding activity. This response to -thrombin was delayed (detectable at 1 hour) compared with the rapid activation (15 to 30 minutes) by platelet-derived growth factor and the cytokine interleukin-6. -Thrombin-induced SIF-A was sensitive to treatment with the tyrosine kinase inhibitor genistein. The thrombin inhibitor hirudin prevented the -thrombin-mediated SIF-A induction. Cycloheximide had no effect on the ability of -thrombin to induce SIF-A, suggesting that induction does not require new protein synthesis. -Thrombin-induced SIF-A could be resolved into two additional subcomplexes termed SIF-A_F and SIF-A_S. Antibodies against Stat3 reacted with -thrombin-induced SIF-A_F, suggesting that Stat3 or a related protein is present in this subcomplex. Induction of SIF-A DNA binding activity may contribute to -thrombin-mediated cellular responses, including wound healing, cell proliferation, and inflammation in the vasculature.

Key Words: thrombin • transcription factors • muscle, smooth, vascular • signal transduction

Abbreviations: Ang II = angiotensin II • IL-6 = interleukin-6 • PDGF = platelet-derived growth factor • SIE = sis-inducing element • SIF-A = sis-inducing factor A • STAT = signal transducers and activators of transcription • VSM = vascular smooth muscle

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