Dibutyl phthalate induces epithelial-mesenchymal transition of renal tubular epithelial cells via the Ang II/AMPKα2/Cx43 signaling pathway.

Xie Zhiwen, Zhang Yongqing, Sun Wenlan, Hua Shan, Han Bangmin, Jiang Juntao, Zhu Yingjian, Jing Yifeng

Toxicology 2023 Aug 01

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Maternal exposure to dibutyl phthalate (DBP) induces renal fibrosis in offspring. However, the specific roles of connexin 43 (Cx43) in DBP-induced renal fibrosis remain unknown. Therefore, in this study, we analysed the expression of Cx43 in renal tubular epithelial cells (RTECs) with or without DBP exposure using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. A small interfering RNA against Cx43 was introduced to assess its role in epithelial-mesenchymal transition (EMT) of RTECs caused by 100 μmol/L DBP. Bioinformatics analysis was conducted with AMP-activated protein kinase (AMPK)-α2 and angiotensin (Ang) II inhibitors to determine the mechanisms involved in the expression of Cx43 in HK-2 cells. RT-qPCR and western blotting revealed that DBP increased the expression of Cx43 in vitro. Moreover, Cx43 knockdown significantly alleviated DBP-induced EMT caused by DBP in HK-2 cells. Bioinformatics analysis with AMPKα2 and Ang II inhibitors revealed that DBP upregulated Cx43 expression by activating the Ang II/AMPKα2 signaling pathway. Our findings indicate that DBP induces renal fibrosis by activating Ang II/AMPKα2/Cx43 signaling pathway and EMT in RETCs, suggesting a potential target for the treatment of renal fibrosis. Copyright © 2023. Published by Elsevier B.V.

Citation

Xie Zhiwen, Zhang Yongqing, Sun Wenlan, Hua Shan, Han Bangmin, Jiang Juntao, Zhu Yingjian, Jing Yifeng. Dibutyl phthalate induces epithelial-mesenchymal transition of renal tubular epithelial cells via the Ang II/AMPKα2/Cx43 signaling pathway. Toxicology. 2023 Aug 01;494:153584