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The potential role of aquaporin 1 on aristolochic acid I induced epithelial mesenchymal transition on HK‐2 cells
Author(s) -
Li Ji,
Zhang Mincheng,
Mao Yong,
Li Yimao,
Zhang Xiaoxia,
Peng Xuehan,
Yu Feng
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26310
Subject(s) - aristolochic acid , smad , epithelial–mesenchymal transition , signal transduction , aquaporin 1 , transforming growth factor , chemistry , microbiology and biotechnology , western blot , biology , cancer research , biochemistry , downregulation and upregulation , water channel , mechanical engineering , genetics , gene , engineering , inlet
Aristolochic acid I (AA‐I), one of the main active components in Aristolochaia herbs, may induce aristolochic acid nephropathy (AAN). Renal interstitial fibrosis is one of the most typical features of AAN. To investigate the mechanism of Aristolochic acid I (AA‐I) −induced renal epithelial‐mesenchymal transition (EMT) and determine the role of aquaporin‐1 (AQP1) in this process, we established an AA‐I‐induced EMT model in human proximal tubular epithelial cells (HK‐2 cells). Morphological examination, MTT assay, and Western blot analysis were performed. Aquaporin 1 (AQP1) and several EMT‐related proteins were detected, thereby suggesting the occurrence of AA‐I‐induced EMT. Two main pathways of transforming growth factor‐β (TGF‐β) signaling, namely, Smad‐dependent and Smad‐independent signaling pathways, were also detected. The results showed that the TGF‐β / Smad‐independent signaling pathways (β‐catenin, Ras‐Raf‐Erk1/2 signaling pathways) were activated, and AQP1 expression was decreased during the AA‐I induced EMT on HK‐2 cells. With the presence of TGF‐β1 receptor inhibitor (LY364947) and Erk1/2 inhibitor (PD98059), AQP1 expression was altered by PD98059, suggested that AQP1 could be adjusted by Erk1/2 signaling. Moreover, the inhibitory effect of AA‐I on AQP1 was stronger than that of TGF‐β1, suggested that AQP1 may be an important target on AAN clinical therapy.