AdipoRon Attenuates Hypertension-Induced Epithelial-Mesenchymal Transition and Renal Fibrosis via Promoting Epithelial A
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ORIGINAL ARTICLE
AdipoRon Attenuates Hypertension-Induced Epithelial-Mesenchymal Transition and Renal Fibrosis via Promoting Epithelial Autophagy Yan Li 1 & Bei Song 2 & Chengchao Ruan 3 & WenJie Xue 4 & Jianrong Zhao 1 Received: 29 June 2020 / Accepted: 23 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Hypertension-induced epithelial-mesenchymal transition (EMT) is a major mechanism of renal fibrosis. Adiponectin protects against hypertension-induced target organ damage. AdipoRon is an orally active synthetic adiponectin receptor agonist. However, it is unclear whether AdipoRon could attenuate EMT and renal fibrosis in hypertensive mice. C57BJ/6J mice were utilized to induce DOCA-salt-sensitive hypertensive model. Hypertension results in an altered adiponectin expression and promotes EMT in the kidney. In vitro, AdipoRon inhibits aldosterone (Aldo)-induced EMT and promotes autophagic flux in HK-2 epithelial cells. Mechanically, AdipoRon activates AMPK/ULK1 pathway in epithelial cells. Blockade of AMPK activation, as well as inhibition of autophagy, blocks the effects of AdipoRon on Aldo-induced EMT. Moreover, AdipoRon treatment promotes autophagy and improves renal fibrosis in DOCA-salt-hypertensive mice. Our data suggest that AdipoRon could be a potential therapeutic option to prevent renal fibrosis in hypertensive patients. Keywords Epithelial-mesenchymal transition . AdipoRon . Hypertension . Renal fibrosis . Autophagy
Introduction Hypertension-induced renal fibrosis, characterized as tubulointerstitial fibrosis, tubular atrophy, and glomerulosclerosis, leads to destruction of renal parenchyma and ultimate end-stage renal disease [1, 2]. Emerging evidence Yan Li and Bei Song contributed equally to this work. Associate Editor Nicola Smart oversaw the review of this article * WenJie Xue [email protected] * Jianrong Zhao [email protected] 1
Department of Cardiology, RuiJin Hospital/LuWan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, China
2
Department of General Practice, RuiJin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
3
State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
4
Huangpu District Bansongyuan Road Health Service Center, Shanghai, China
has established epithelial-mesenchymal transition (EMT) as a major mechanism of tubulointerstitial fibrosis [3]. EMT defines a phenotypic conversion in epithelial cells, leading to the loss of epithelial cell-cell-basement membrane contacts and structural/functional polarity and the acquisition of a fibroblastic phenotype [4, 5]. Therefore, inhibition of EMT may be a feasible strategy for the intervention of hypertensioninduced renal fibrosis. Autophagy is the cell biology process in which cytoplasmic components are degraded in lysosomes to maintain cellular homeostasis and energy production [6]. Growing evidence suggests that autophagy activity is required for the homeostasis, viability, and p
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