Abstract:
:Cardiac hypertrophy is accompanied by excessive collagen deposition in the heart. Despite painstaking research on this fatal disease, the precise role of molecular chaperones in myocardial fibrosis has not yet been elucidated. In this study, we have analyzed the mechanism by which Heat shock protein 90 (Hsp90)/Cell division cycle 37 (Cdc37) assembly modulates cardiac hypertrophy associated fibrosis. For the in vitro hypertrophy model, Angiotensin II (AngII) treated cultured adult cardiac fibroblasts were used, whereas the in vivo hypertrophy model was generated by renal artery ligation in adult male Wistar rats (Rattus norvegicus). Pretreatment with the Hsp90 inhibitor or the blocking of Hsp90-Cdc37 interactions during pressure overload hypertrophy resulted in ubiquitin-mediated proteasomal degradation of TGFβ receptor-II (TβR-II) leading to termination of TGFβ mediated signaling. In both cases significant reduction in collagen synthesis was observed revealing the Hsp90/Cdc37 complex as an integral profibrotic component of TGFβ signaling during cardiac hypertrophy.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Datta R,Bansal T,Rana S,Datta K,Chattopadhyay S,Chawla-Sarkar M,Sarkar Sdoi
10.1016/j.cellsig.2015.09.005subject
Has Abstractpub_date
2015-12-01 00:00:00pages
2410-24issue
12eissn
0898-6568issn
1873-3913pii
S0898-6568(15)00267-3journal_volume
27pub_type
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