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Published on: October 23, 2018
TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2
Langen Zhuang1, Guoxi Jin1, Xiaolei Hu1
1Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
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.
Insights
Tetraspanin 8 (TSPAN8) mitigates high glucose-induced cell damage in diabetic nephropathy. Overexpression of TSPAN8 reduces cell death and autophagy, suggesting its potential as a therapeutic target for diabetic kidney disease.
Area of Science:
- Cell Biology
- Molecular Biology
- Nephrology
Background:
- Tetraspanin 8 (TSPAN8) plays roles in cell signaling and development.
- Its involvement in diabetic nephropathy (DN) progression is not well understood.
Purpose of the Study:
- To investigate the role of TSPAN8 in high glucose (HG)-induced autophagy and apoptosis in HK-2 cells.
- To explore TSPAN8's potential as a therapeutic target for DN.
Main Methods:
- RT-PCR and Western Blot to measure TSPAN8 levels.
- CCK-8 assay for cell proliferation and flow cytometry for apoptosis.
- TSPAN8 gene transfection to evaluate functional roles.
Main Results:
- TSPAN8 levels were decreased in DN patients' blood and HG-induced HK-2 cells.
- TSPAN8 overexpression protected HK-2 cells from HG-induced apoptosis.
- TSPAN8 formed a complex with Rictor and mTORC2, suppressing HG-induced autophagy via mTOR activity.
Conclusions:
- TSPAN8 mitigates high glucose-induced autophagy and apoptosis in renal cells.
- TSPAN8 represents a potential therapeutic target for diabetic nephropathy treatment.
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