作者
Chris J Scotton, Malvina A Krupiczojc, Melanie Königshoff, Paul F Mercer, YC Gary Lee, Naftali Kaminski, John Morser, Joseph M Post, Toby M Maher, Andrew G Nicholson, James D Moffatt, Geoffrey J Laurent, Claudia K Derian, Oliver Eickelberg, Rachel C Chambers
发表日期
2009/9/1
期刊
The Journal of clinical investigation
卷号
119
期号
9
页码范围
2550-2563
出版商
American Society for Clinical Investigation
简介
Uncontrolled activation of the coagulation cascade contributes to the pathophysiology of several conditions, including acute and chronic lung diseases. Coagulation zymogens are considered to be largely derived from the circulation and locally activated in response to tissue injury and microvascular leak. Here we report that expression of coagulation factor X (FX) is locally increased in human and murine fibrotic lung tissue, with marked immunostaining associated with bronchial and alveolar epithelia. FXa was a potent inducer of the myofibroblast differentiation program in cultured primary human adult lung fibroblasts via TGF-β activation that was mediated by proteinase-activated receptor–1 (PAR1) and integrin αvβ5. PAR1, αvβ5, and α-SMA colocalized to fibrotic foci in lung biopsy specimens from individuals with idiopathic pulmonary fibrosis. Moreover, we demonstrated a causal link between FXa and fibrosis …
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