@article{81cfc9179d8e41a9849f57bf4106c2d4,
title = "Thrombin induces thrombomodulin mRNA expression via the proteolytically activated thrombin receptor in cultured bovine smooth muscle cells",
abstract = "Thrombin, an important mitogen governing smooth muscle cell proliferation, binds to cultured bovine aortic smooth muscle cells (BASMCs) via both the proteolytically activated thrombin receptor (PATR) and thrombomodulin (TM). Although TM mRNA expression and functional activity is regulated by thrombin in human endothelial cells and mouse hemangioma cells, it remains unclear in those models whether the increased TM mRNA expression observed upon thrombin stimulation is mediated through the activation of PATR or via TM occupancy. We observed in cultured BASMCs that TM mRNA is increased threefold to sixfold by either thrombin, basic fibroblast growth factor (bFGF), or platelet-derived growth factor (PDGF). The increase in TM mRNA with thrombin is time dependent (maximal at 3 hours), a consequence of increased mRNA stability, and accompanied by increases in cell surface TM functional activity. Thrombin-induced TM mRNA was reproduced by the hexameric thrombin receptor-activating peptide (TRAP6) and augmented by a TM-specific antibody. Together, these data suggest that up-regulation of TM mRNA by thrombin is mediated via the PATR. We speculate that increases in BASMC TM mRNA and activity after thrombin may contribute to the impaired thrombus formation observed after atherosclerotic vascular injury.",
author = "Ma, {Shwu Fan} and Garcia, {Joe G.N.} and Ute Reuning and Little, {Sheila P.} and Bang, {Nils U.} and Dixon, {Eric P.}",
note = "Funding Information: From the Department of Physiology and Biophysics, the Department of Pathology and Laboratory Medicine, and the Department of Medicine, Indiana University School of Medicine; and Lilly Research Laboratories, CNS/GI/GU Division. Supported by a fellowship from the American Heart Association, Indiana Affiliate; National Institutes of Health awards HL44746 and NIH 50533; and a Veterans Administration Merit Review Award. Submitted for publication June 18, 1996; revision submitted Nov. 26, 1996; accepted Jan. 6, 1997. Reprint requests: Joe G. N. Garcia, MD, Richard Roudebush VA Medical Center, 1481 W. Tenth St., 111P, Indianapolis, IN 46202. Copyright {\textcopyright} 1997 by Mosby-Year Book, Inc. 0022-2143/97 $5.00 + 0 5/1/80648 ultured BASMCs, like vascular endothe-lium, are endowed with a dual thrombin C receptor system consisting of the PATR and TM. Activation of the PATR, a member of the seven-transmembrane receptor family, 1 results in numerous events crucial to the development of arterial thrombosis 2 and inflammation, 3 such as phospholipase C activation, arachidonate metabolism, and increased vascular permeability secondary to endothelial barrier dysfunction. 4 In cultured SMCs, occupancy of the PATR elicits a strong mitogenic signal, resulting in intimal SMC proliferation. 5",
year = "1997",
month = jun,
doi = "10.1016/S0022-2143(97)90195-5",
language = "English (US)",
volume = "129",
pages = "611--619",
journal = "Journal of Laboratory and Clinical Medicine",
issn = "0022-2143",
publisher = "Elsevier Inc.",
number = "6",
}