Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney
- Department of Nephrology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240 (China)
- Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China)
- School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China)
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.
- OSTI ID:
- 22648603
- Journal Information:
- Experimental Cell Research, Vol. 346, 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); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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