Rapamycin Reduces Podocyte Apoptosis and is Involved in Autophagy and mTOR/ P70S6K/4EBP1 Signaling

Rapamycin Reduces Podocyte Apoptosis and is Involved in Autophagy and mTOR/ P70S6K/4EBP1 Signaling

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Background/Aims: The purpose of this study was to investigate the impact of rapamycin (RAP) on autophagy in podocytes and the therapeutic effects of RAP on idiopathic membranous nephropathy (IMN).Methods: We established an in vitro model of IMN by preconditioning mouse podocytes with puromycin aminonucleoside (PAN).A Cell Counting Kit-8 was used to detect the proliferation of each group of podocytes.Podocyte apoptosis was analyzed by flow cytometry via annexin V/propidium iodide dual staining.Subsequently, we earthbath facial wipes observed the number of autophagosomes by transmission electron microscopy.

Western blotting was used to detect the levels of LC3, mTOR, p-mTOR, 4EBP1, p-4EBP1, P70S6K, and p-P70S6K in each group.Results: The number of podocytes in the PAN + 100 ng/mL RAP group, PAN + 200 ng/mL RAP group, and PAN + 300 ng/mL RAP group was significantly increased (P < 0.01).The click here apoptotic rate of podocytes was significantly different between the PAN group and the PAN + RAP group (P < 0.001).

There were fewer autophagic corpuscles in the PAN group and more autophagosomes were observed in the PAN + RAP group.LC3 protein expression was down-regulated in the PAN group, while its expression was up-regulated in the PAN + RAP group.In the PAN group, the levels of phosphorylated mTOR, 4EBP1, and P70S6K were increased, while in the PAN + RAP group, protein phosphorylation was reduced.Conclusions: RAP can effectively inhibit the mTOR/P70S6K/4EBP1 signaling pathway, and activate podocyte autophagy, consequently reducing podocyte apoptosis.Therefore, RAP could be used for the treatment of idiopathic membranous nephropathy.