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Published on: August 23, 2024
SIRT2 Affects Cell Proliferation and Apoptosis by Suppressing the Level of Autophagy in Renal Podocytes
Shuang Liu1, Xiangfu Gao2, Zhenliang Fan3
1Geriatrics, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Purpose:
Despite the discovery of many important molecules in diabetic nephropathy, there has been very limited progress in the management of diabetic kidney diseases and the design of new drugs. To fill this gap, the present study explored the expression of SIRT2 in high-glucose murine kidney foot cells and its impact on cell biological functions.
Methods:
Expression levels of SIRT2 in the MPC-5 of murine kidney foot cells after high and normal glucose treatment or in cells targeted with siRNA were detected using qRT-PCR. Cellular proliferation and programmed cell death were analyzed via the CCK8 assay and flow cell technique, separately. Levels of autophagy markers were measured by western blotting, and chloroquine treatment was applied to the cells to observe the effect of SIRT2 on cell proliferation and apoptosis after treatment.
Results:
The expression level of SIRT2 was remarkably upregulated in the high-GLU group in contrast to the low-GLU group. The cell proliferation and autophagy levels were significantly reduced, and apoptosis was remarkably reinforced in the high-GLU group in contrast to the normal GLU group. However, knocking down the expression level of SIRT2 caused an increase in cell proliferation and cell autophagy levels and significantly weakened apoptosis. Chloroquine influenced cell proliferation and apoptosis in cells targeted with SIRT2 siRNA.
Conclusion:
SIRT2 expression was upregulated in hyperglycaemic murine kidney foot cells, and knocking down the expression level of SIRT2 affected the biological function of the cells. We found that SIRT2 may modulate cell proliferation and apoptosis by regulating cell autophagy.
Insights
SIRT2 expression increases in high glucose conditions, impairing kidney cell function. Reducing SIRT2 improves cell proliferation and autophagy, suggesting it as a therapeutic target for diabetic kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Diabetic nephropathy management remains challenging despite molecular discoveries.
- Limited progress in drug design for diabetic kidney diseases necessitates novel therapeutic targets.
Purpose of the Study:
- To investigate the expression of SIRT2 in high-glucose murine kidney cells.
- To determine the impact of SIRT2 on kidney cell biological functions, including proliferation, apoptosis, and autophagy.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to detect SIRT2 expression.
- CCK8 assay and flow cytometry for cell proliferation and apoptosis analysis.
- Western blotting for autophagy markers and chloroquine treatment to assess SIRT2's role.
Main Results:
- SIRT2 expression was significantly upregulated in high-glucose conditions.
- High glucose reduced cell proliferation and autophagy while increasing apoptosis.
- Knocking down SIRT2 reversed these effects, enhancing proliferation and autophagy and reducing apoptosis.
Conclusions:
- SIRT2 is upregulated in hyperglycemic kidney cells and influences cell proliferation and apoptosis.
- SIRT2 may regulate cell autophagy, presenting a potential therapeutic pathway for diabetic kidney disease.
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