Thrombin stimulates fibroblast procollagen production via proteolytic activation of protease-activated receptor 1

• DOI: 10.1042/bj3330121
• Publication Date: 2015-08-10T22:02:23Z
• Authors: Rachel C. CHAMBERS; Karim DABBAGH; Robin J. McANULTY; Andy J. GRAY; Olivier P. BLANC-...; Geoffrey J. LAURENT
• Keywords: Hirudin; Procollagen peptidase; Thrombin receptor

Thrombin is a multifunctional serine protease that has crucial role in blood coagulation. It also potent mesenchymal cell mitogen and chemoattractant might therefore have an important the recruitment local proliferation of cells at sites tissue injury. We hypothesized thrombin affect deposition connective proteins these by directly stimulating fibroblast procollagen production. To address this hypothesis, effect on production gene expression human foetal lung fibroblasts was assessed over 48 h. stimulated concentrations 1 nM above, with maximal increases between 60% 117% 10 thrombin. These effects were, least part, due to increased steady-state levels α1(I) mRNA. They could furthermore be reproduced receptor-activating peptides for protease-activated receptor (PAR-1) were completely abolished when rendered proteolytically inactive specific inhibitors d-Phe-Pro-ArgCH2Cl hirudin, indicating mediating via proteolytic activation PAR-1. results suggest influence during normal wound healing development fibrosis