Dibutyl phthalate induces epithelial-mesenchymal transition of renal tubular epithelial cells via the Ang II/AMPK alpha 2/Cx43 signaling pathway

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 mu mol/L DBP. Bioinformatics analysis was conducted with AMP-activated protein kinase (AMPK)-alpha 2 and angiotensin (Ang) II inhibitors to determine the mechanisms involved in the expression of Cx43 in HK-2 cells. RTqPCR 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 AMPK alpha 2 and Ang II inhibitors revealed that DBP upregulated Cx43 expression by activating the Ang II/AMPK alpha 2 signaling pathway. Our findings indicate that DBP induces renal fibrosis by activating Ang II/AMPK alpha 2/Cx43 signaling pathway and EMT in RETCs, suggesting a potential target for the treatment of renal fibrosis.

Automated summary

Maternal exposure to dibutyl phthalate (DBP) induces renal fibrosis in offspring. The study investigated the role of connexin 43 (Cx43) in DBP-induced renal fibrosis. The results showed that DBP increased the expression of Cx43 in renal tubular epithelial cells (RTECs), and silencing Cx43 alleviated DBP-induced epithelial-mesenchymal transition (EMT) in HK-2 cells. Bioinformatics analysis revealed that DBP upregulated Cx43 expression through the Ang II/AMPK alpha 2 signaling pathway. These findings suggest that targeting Cx43 and the Ang II/AMPK alpha 2 pathway may be a potential treatment for renal fibrosis.