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Unraveling the Molecular Mechanism behind Thrombin Induced Myofibrobast Transition
Author(s) -
Meyer Jennifer Ashley,
Strande Jennifer
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.972.12
Subject(s) - thrombin , transactivation , thrombin receptor , receptor , microbiology and biotechnology , chemistry , signal transduction , downregulation and upregulation , mediator , biology , biochemistry , immunology , transcription factor , platelet , gene
TGF‐β1 is a mediator in fibrosis by activating its downstream Smad signaling pathway, where they are translocated to the nucleus. TGF‐ β has also been shown to inhibit thrombin signaling. Thrombin has been shown to act via the PAR1 receptor, a G‐protein coupled receptor. Activation of PAR1 by thrombin results in many profibrotic effects of thrombin via the induction and activation of secondary mediators including upregulation of TGF‐β and procollagen. Therefore, we hypothesize that thrombin promotes myofibroblast formation through a TGF‐ β independent/dependent pathway. Cells treated with thrombin showed an increase in α‐SMA compared to control. Inhibition of all G‐protein coupled receptors resulted in a complete abolition of fluorescent intensity, indicating that the mechanism by which thrombin induces fibrosis is via G‐proteins, yet inhibition of individual G‐proteins did not have this effect, indicating a potential additive effect. Thrombin treatment also results in increased translocation of Smad2 and 3 to the nucleus. Our results suggest a possible transactivation of the TGF‐ β receptor by the PAR1 receptor. Ongoing experiments will further elucidate the mechanism behind thrombin induced fibrosis.