Abstract
INTRODUCTION: The objective of the study was to observe whether Cx43 could regulate EMT of RTECs by influencing Akt/mTOR signaling pathway, and whether ASV could inhibit the development of renal interstitial fibrosis by regulating Cx43. METHODS: Lentivirus infection was transfected into RTECs with the final concentration of 50×PFU/ cell to regulate the expression of Cx43.And RTECs were intervened by different doses of ASV. After synchronous culture of RTECs in each group,cell morphological changes were observed and the expression levels of EMT-related indicators, and the expression levels of Cx43, the protein expressions and phosphorylation levels AKT and mTOR in different groups were detected by WB. RESULTS: When the expression of Cx43 in RTECs was regulated by lentivirus infection, the degree of EMT induced by TGF‑β1 and the phosphorylation level of Akt and mTOR were changed accordingly, indicating that Akt/mTOR pathway might be a downstream molecular mechanism by which Cx43 could regulate EMT. After intervention with different doses of ASV, the expression level of Cx43 increased with obvious concentration dependence, and the expression levels of p-Akt and p- mTOR were significantly altered, suggesting that ASV could effectively increase the protein expressions of TGF‑β1-induced Cx43 in RTECs and inhibit the phosphorylation levels of Akt and mTOR. CONCLUSION: Cx43 is the main material basis of RTECs’injury, and ASV could inhibit TGF-β1 induced RTECs transdifferentiation. In-depth study of the mechanism may provide a broad application prospect for the treatment of renal interstitial fibrosis.
Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition: Role of Plasmin-Activated Signals