TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2.

ABSTRACT

TSPAN8 mediates signal transduction from extracellular cues and regulates cell development, activation, growth, and motility. However, whether TSPAN8 is involved in the progression of diabetic nephropathy (DN) remains unclear. This study aimed to explore the potential functional roles of TSPAN8 in regulating autophagy and apoptosis of HK-2 cells induced by high glucose (HG). RT-PCR and western blot analysis (WB) were employed to detect TSPAN8 levels in the blood samples of DN patients as well as in HG-induced HK-2 cells. Cell proliferation of HK-2 cells was examined by CCK-8 assay, and apoptosis was analyzed by flow cytometry. The functional role of TSPAN8 was evaluated by the transfection of TSPAN8 expression plasmid. Results showed that TSPAN8 level was significantly reduced in the blood samples of DN patients and HG-induced HK-2 cell lines. TSPAN8 overexpression rescued HG-induced apoptosis in HK-2 cells. TSPAN8 could form a complex with Rictor and mTORC2. TSPAN8 overexpression suppressed HG-induced autophagy in HK-2 cells, which was dependent on mTOR activity. In conclusion, the present study showed that TSPAN8 mitigates HG-induced autophagy and apoptosis in HK-2 cells, which may serve as candidate target for DN treatment.