Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10814798 | Cellular Signalling | 2015 | 30 Pages |
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.
Keywords
β-MHCANFANGIIECMLVDdp38MAPKHDAC-1SMADCOL-1STAT-3Cdc37RRL17AAGCOL-3TAK-1%FSpercentage fractional shorteningTβR-IIGAPDHHRPTGFβERKHSP90RT-PCR17-allylamino-17-demethoxygeldanamycinDMSOPSI-BLASTsiRNAangiotensin-IIAngiotensin IIAktSimple modular architecture research toolEDTAethylenediamine tetra acetic acidsodium dodecyl sulfate-polyacrylamide gel electrophoresisSDS-PAGETransforming growth factor βTAEsilencing RNADimethyl sulfoxiderabbit reticulocyte lysateextracellular signal regulated kinaseleft ventricular diastolic diameterExtracellular matrixSMARTCardiac hypertrophyReverse transcriptase-polymerase chain reactionhorse radish peroxidaseHeat shock protein 90protein kinase Bp38 mitogen activated protein kinaseCollagenglyceraldehyde 3 phosphate dehydrogenase
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Authors
Ritwik Datta, Trisha Bansal, Santanu Rana, Kaberi Datta, Shiladitya Chattopadhyay, Mamta Chawla-Sarkar, Sagartirtha Sarkar,