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Evidence-Based Complementary and Alternative Medicine
Volume 2017, Article ID 9596256, 13 pages
https://doi.org/10.1155/2017/9596256
Research Article

Aristolochic Acid-Induced Autophagy Promotes Epithelial-to-Myofibroblast Transition in Human Renal Proximal Tubule Epithelial Cells

Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

Correspondence should be addressed to Yi-Pu Chen; nc.moc.liamdem@upiy_nehc

Received 29 April 2017; Revised 10 August 2017; Accepted 5 September 2017; Published 18 October 2017

Academic Editor: Cheorl-Ho Kim

Copyright © 2017 Yu-Lin Man et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial-to-myofibroblast transition (EMT). However, the relationship between AA-induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation. The enhancement of autophagy using autophagy inducers, rapamycin or serum-free medium, led to an aggravation of EMT and upregulated expression of fibronectin, a component of extracellular matrix, in AA-treated HKC cells. In contrast, the inhibition of autophagy by autophagy inhibitor, 3-methyladenine, or by knockdown of Beclin 1 led to an attenuation of EMT and downregulated expression of fibronectin in AA-treated HKC cells. Taken together, our study suggests that, after AA stimulation, two types of cell responses of HKC cells, autophagy and EMT, will successively appear, and autophagy can promote EMT of HKC.