title: Hsp90/Cdc37 assembly modulates TGFβ receptor-II to act as a profibrotic regulator of TGFβ signaling during cardiac hypertrophy.
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.
authors.affiliation: Genetics and Molecular Cardiology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata-700 019, India. Electronic address: rdatta30@gmail.com.
authors.forename: Ritwik
authors.initials: R
authors.lastname: Datta
authors.affiliation: Genetics and Molecular Cardiology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata-700 019, India. Electronic address: teesta.06@gmail.com.
authors.forename: Trisha
authors.initials: T
authors.lastname: Bansal
authors.affiliation: Genetics and Molecular Cardiology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata-700 019, India. Electronic address: rana.santanu@gmail.com.
authors.forename: Santanu
authors.initials: S
authors.lastname: Rana
authors.affiliation: Genetics and Molecular Cardiology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata-700 019, India. Electronic address: kaberidatta@gmail.com.
authors.forename: Kaberi
authors.initials: K
authors.lastname: Datta
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road Scheme-XM, Beliaghata, Kolkata-700010, India. Electronic address: shiladitya_bio@yahoo.co.in.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road Scheme-XM, Beliaghata, Kolkata-700010, India. Electronic address: chawlam70@yahoo.com.
authors.forename: Mamta
authors.initials: M
authors.lastname: Chawla-Sarkar
authors.affiliation: Genetics and Molecular Cardiology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata-700 019, India. Electronic address: sagartirtha.sarkar@gmail.com.
authors.forename: Sagartirtha
authors.initials: S
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D017208:Rats, Wistar; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; C103269:Cdc37 protein, rat; D018797:Cell Cycle Proteins; D018841:HSP90 Heat-Shock Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Angiotensin-II; Cardiac hypertrophy; Cdc37; Collagen; Hsp90; TGFβ receptor-II