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α 2 ‐Antiplasmin is involved in the production of transforming growth factor β 1 and fibrosis
Author(s) -
KANNO Y.,
KUROKI A.,
OKADA K.,
TOMOGANE K.,
UESHIMA S.,
MATSUO O.,
MATSUNO H.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02745.x
Subject(s) - fibrosis , transforming growth factor , extracellular matrix , bleomycin , plasmin , cancer research , transforming growth factor beta , immunology , growth factor , biology , microbiology and biotechnology , chemistry , medicine , pathology , biochemistry , chemotherapy , receptor , enzyme
Summary. Background: Fibrotic disease occurs in most tissues. Transforming growth factor (TGF)‐β is the major inducer of fibrosis. The fibrinolytic system is considered to play an important role in the degradation of extracellular matrices. However, the detailed mechanism of how this system affects fibrosis remains unclear. Methods and results: We examined experimental fibrosis in mice with a deficiency of α 2 ‐antiplasmin (α2AP), which is a potent and specific plasmin inhibitor. We found that the lack of α2AP attenuated bleomycin‐induced TGF‐β 1 synthesis and fibrosis. In addition, the production of TGF‐β 1 from the explanted fibroblasts of α2AP −/− mice decreased dramatically as compared to that in wild‐type mice. Moreover, we found that α2AP specifically induces the production of TGF‐β 1 in fibroblasts. Conclusion: The lack of α2AP attenuated TGF‐β 1 synthesis, thereby resulting in attenuated fibrosis. This is the first report to describe the crucial role that α2AP plays in TGF‐β 1 synthesis during the process of fibrosis. Our results provide new insights into the role of α2AP in fibrosis.