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	Ritwik Datta, Trisha Bansal, Santanu Rana, Kaberi Datta, Shiladitya Chattopadhyay, Mamta Chawla-Sarkar, Sagartirtha Sarkar
Journal	Cellular signalling (Cell Signal) Vol. 27 Issue 12 Pg. 2410-24 (Dec 2015) ISSN: 1873-3913 [Electronic] England
PMID	26362850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References	Carrier Proteins Cdc37 protein, rat Cell Cycle Proteins HSP90 Heat-Shock Proteins Receptors, Transforming Growth Factor beta Transforming Growth Factor beta Collagen Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II
Topics	Animals Cardiomegaly (metabolism) Carrier Proteins (physiology) Cell Cycle Proteins (physiology) Cells, Cultured Collagen (genetics, metabolism) Fibroblasts (metabolism) Gene Expression HSP90 Heat-Shock Proteins (physiology) Male Protein Serine-Threonine Kinases (metabolism) Protein Stability Proteolysis Rats, Wistar Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta (metabolism) Signal Transduction Transcriptional Activation Transforming Growth Factor beta (physiology) Ubiquitination

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!