Rapamycin reduces podocyte damage by inhibiting the PI3K/AKT/mTOR signaling pathway and promoting autophagy. (17th February 2022) - Yu, Shengyou
Objective: Rapamycin is a potent inducer of autophagy in podocytes. However, we still understand very little about how autophagy is regulated under podocyte injury conditions. This study aimed to investigate the role of autophagy in podocyte injury and the regulatory mechanism of the PI3K/Akt/mTOR signaling pathway in this process. Methods: The podocytes were cultured in vitro, and the apoptosis rate of each group was determined by flow cytometry. The protein expression and distribution of LC3-II were examined by immunofluorescence. The phosphorylation levels of Akt, LC3-II, mTOR, 4EBP1, and P70S6K were measured using Western Blot. Transmission electron microscopy was used to examine the changes in autophagosomes in each group. Results: Compared with the control group, the puromycin group (PAN) increased podocyte apoptosis, decreased numbers of autophagosomes, and downregulated LC3-II protein expression. Compared with the PAN group, the podocyte apoptosis rate decreased in the Rapamycin group (RAPA), the number of autophagosomes increased, and LC3-II protein expression was upregulated. In addition, PAN evoked an increase in p-Akt expressions, RAPA treatment induced a reversal of PAN-induced p-Akt upregulation, and the phosphorylation levels of mTOR, 4EBP1, and P70S6K were downregulated. Conclusion: PAN can damage podocytes by inhibiting podocyte autophagic activity and promoting apoptosis. Rapamycin can ameliorate PAN-induced podocyte damage by activating autophagy. This effect may be related to rapamycin-mediated PI3K/AKT/mTOR signaling pathway and autophagy.