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Title: Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney

Abstract

Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights:more » • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.« less

Authors:
; ;  [1];  [2];  [1];  [3];  [1];  [4]
  1. Department of Nephrology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240 (China)
  2. Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China)
  3. School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China)
  4. (China)
Publication Date:
OSTI Identifier:
22648603
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 346; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALDOSTERONE; ANIMAL TISSUES; CELL PROLIFERATION; COLLAGEN; COMPARATIVE EVALUATIONS; DISEASES; FIBROSIS; GROWTH FACTORS; HAZARDS; HYPERTROPHY; INHIBITION; KIDNEYS; MATRICES; MIGRATION; OXIDATION; PHOSPHORYLATION; PHOSPHOTRANSFERASES; PLANT GROWTH; PLANT TISSUES; POTENTIALS; RATS; RECEPTORS; SIGNALS; STRESSES; TYROSINE

Citation Formats

Sheng, Lili, Yang, Min, Ding, Wei, Zhang, Minmin, Niu, Jianying, Qiao, Zhongdong, Gu, Yong, E-mail: yonggu@vip.163.com, and Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240. Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.06.009.
Sheng, Lili, Yang, Min, Ding, Wei, Zhang, Minmin, Niu, Jianying, Qiao, Zhongdong, Gu, Yong, E-mail: yonggu@vip.163.com, & Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240. Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney. United States. doi:10.1016/J.YEXCR.2016.06.009.
Sheng, Lili, Yang, Min, Ding, Wei, Zhang, Minmin, Niu, Jianying, Qiao, Zhongdong, Gu, Yong, E-mail: yonggu@vip.163.com, and Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240. 2016. "Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney". United States. doi:10.1016/J.YEXCR.2016.06.009.
@article{osti_22648603,
title = {Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney},
author = {Sheng, Lili and Yang, Min and Ding, Wei and Zhang, Minmin and Niu, Jianying and Qiao, Zhongdong and Gu, Yong, E-mail: yonggu@vip.163.com and Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240},
abstractNote = {Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights: • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.},
doi = {10.1016/J.YEXCR.2016.06.009},
journal = {Experimental Cell Research},
number = 1,
volume = 346,
place = {United States},
year = 2016,
month = 8
}
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