TY - JOUR AB - Podocyte injury, which promotes progressive nephropathy, is considered a key factor in the progression of diabetic nephropathy. The mammalian target of rapamycin (mTOR) signaling cascade controls cell growth, survival and metabolism. The present study investigated the role of mTOR signaling in regulating high glucose (HG)‑induced podocyte injury. MTT assay and flow cytometry assay results indicated that HG significantly increased podocyte viability and apoptosis. HG effects on podocytes were suppressed by mTOR complex 1 (mTORC1) inhibitor, rapamycin, and further suppressed by dual mTORC1 and mTORC2 inhibitor, KU0063794, when compared with podocytes that received mannitol treatment. In addition, western blot analysis revealed that the expression levels of Thr‑389‑phosphorylated p70S6 kinase (p‑p70S6K) and phosphorylated Akt (p‑Akt) were significantly increased by HG when compared with mannitol treatment. Notably, rapamycin significantly inhibited HG‑induced p‑p70S6K expression, but did not significantly impact p‑Akt expression. However, KU0063794 significantly inhibited the HG‑induced p‑p70S6K and p‑Akt expression levels. Furthermore, the expression of ezrin was significantly reduced by HG when compared with mannitol treatment; however, α‑smooth muscle actin (α‑SMA) expression was significantly increased. Immunofluorescence analysis on ezrin and α‑SMA supported the results of western blot analysis. KU0063794, but not rapamycin, suppressed the effect of HG on the expression levels of ezrin and α‑SMA. Thus, it was suggested that the increased activation of mTOR signaling mediated HG‑induced podocyte injury. In addition, the present findings suggest that the mTORC1 and mTORC2 signaling pathways may be responsible for the cell viability and apoptosis, and that the mTORC2 pathway could be primarily responsible for the regulation of cytoskeleton‑associated proteins. AD - Nephrology Department, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China AU - Li,Qiuyue AU - Zeng,Yan AU - Jiang,Qing AU - Wu,Cong AU - Zhou,Jing DA - 2019/04/01 DO - 10.3892/etm.2019.7236 EP - 2502 IS - 4 JO - Exp Ther Med KW - mammalian target of rapamycin complex 1 mammalian target of rapamycin complex 2 podocyte injury high glucose diabetic nephropathy PY - 2019 SN - 1792-0981 1792-1015 SP - 2495 ST - Role of mTOR signaling in the regulation of high glucose‑induced podocyte injury T2 - Experimental and Therapeutic Medicine TI - Role of mTOR signaling in the regulation of high glucose‑induced podocyte injury UR - https://doi.org/10.3892/etm.2019.7236 VL - 17 ER -