Thrombin induces thrombomodulin mRNA expression via the proteolytically activated thrombin receptor in cultured bovine smooth muscle cells

Shwu Fan Ma, Joe GN Garcia, Ute Reuning, Sheila P. Little, Nils U. Bang, Eric P. Dixon

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)611-619
Number of pages9
JournalThe Journal of Laboratory and Clinical Medicine
Volume129
Issue number6
StatePublished - Jun 1997
Externally publishedYes

Fingerprint

Thrombin Receptors
Thrombomodulin
Thrombin
Smooth Muscle Myocytes
Muscle
Cells
Messenger RNA
thrombin receptor peptide SFLLRNP
Thrombin Time
Vascular System Injuries
Platelet-Derived Growth Factor
Endothelial cells
RNA Stability
Cell proliferation
Fibroblast Growth Factor 2
Hemangioma
Mitogens
Thrombosis
Up-Regulation
Endothelial Cells

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Thrombin induces thrombomodulin mRNA expression via the proteolytically activated thrombin receptor in cultured bovine smooth muscle cells. / Ma, Shwu Fan; Garcia, Joe GN; Reuning, Ute; Little, Sheila P.; Bang, Nils U.; Dixon, Eric P.

In: The Journal of Laboratory and Clinical Medicine, Vol. 129, No. 6, 06.1997, p. 611-619.

Research output: Contribution to journalArticle

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