HSP70 inhibits high glucose-induced Smad3 activation and attenuates epithelial-to-mesenchymal transition of peritoneal mesothelial cells

Liu,Jun; Bao,Jinfang; Hao,Jing; Peng,Yan; Hong,Fuyuan

doi:10.3892/mmr.2014.2279

HSP70 inhibits high glucose-induced Smad3 activation and attenuates epithelial-to-mesenchymal transition of peritoneal mesothelial cells

Authors:
- Jun Liu
- Jinfang Bao
- Jing Hao
- Yan Peng
- Fuyuan Hong
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Affiliations: Department of Nephrology, The First People's Affiliated Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China, Department of Nephrology, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: May 28, 2014 https://doi.org/10.3892/mmr.2014.2279
Pages: 1089-1095

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Abstract

Heat shock proteins (HSPs) are molecular chaperones that were initially identified as proteins expressed following exposure of cells to environmental stress. However, the function of HSPs in epithelial‑to‑mesenchymal transition (EMT) of peritoneal mesothelial cells remains unknown. In the present study, the regulation of HSPs and their function in cell EMT, particularly in rat peritoneal mesothelial cells (RPMCs), and the surrounding glucose concentrations and the molecular mechanism involved were investigated. This study explored the effect of HSP70 on high glucose (HG)-induced EMT by overexpression and small interfering RNA (siRNA) knockdown of HSP70, as well as the underlying molecular mechanisms. It was found that HSP70 inhibits HG-induced EMT by modulating Smad expression and activation. HSP70 overexpression inhibited phosphorylation and nuclear translocation of p-Smad3 and p-Smad4, while siRNA of HSP70 enhanced HG‑induced Smad3 and Smad4 phosphorylation and EMT. Furthermore, HSP70 suppressed EMT by inhibiting the generation of reactive oxygen species (ROS) induced by HG. In conclusion, HSP70 inhibits EMT of peritoneal mesothelial cells primarily by exerting domain‑specific effects on Smad3 and Smad4 activation and reducing the release of ROS. HSP70 may be a novel therapeutic target for peritoneal dialysis patients with peritoneal fibrosis.

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