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Published on: August 23, 2024
Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy
Tao Wang1, Yanbin Gao1,2, Xiaolei Wang1
1School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.
Background:
Diabetic nephropathy (DN) is a progressive microvascular complication of diabetes mellitus (DM), driven largely by podocyte apoptosis. The cysteine protease Calpain 10 is known to augment apoptosis and necrosis, and is a potential therapeutic target in DN.
Methods:
Type 2 diabetes was induced in SD rats by high-fat diet (HFD) feeding and streptozotocin (STZ) injections, and simulated in vitro by culturing conditionally immortalized mouse podocytes in hyperlipidemic (PA, 100 μM) conditions. The rate of apoptosis in the renal tissues and cultured podocytes was determined by TUNEL assay. The expression of Calpain 10 and its biological effects were assayed by real-time PCR, Western blotting, immunofluorescence and electron microscopy.
Results:
Calpain 10 was up-regulated in the kidneys of DN rats, as well as immortalized mouse podocytes. High levels of Calpain 10 was associated with renal dysfunction and tissue destruction, and podocyte injury and apoptosis. Knockdown of Calpain 10 protected podocytes by decreasing apoptosis rate, and upregulated nephrin.
Conclusion:
Calpain 10 is a pro-apoptotic factor in DN, and can be targeted for treating glomerular diseases.
Insights
Calpain 10 promotes apoptosis in diabetic nephropathy (DN). Inhibiting Calpain 10 protects podocytes, offering a potential therapeutic strategy for DN and other glomerular diseases.
Area of Science:
- Nephrology
- Molecular Biology
- Diabetology
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM), characterized by podocyte apoptosis.
- Calpain 10, a cysteine protease, exacerbates apoptosis and necrosis, making it a potential therapeutic target in DN.
Purpose of the Study:
- To investigate the role of Calpain 10 in diabetic nephropathy.
- To assess the therapeutic potential of targeting Calpain 10 for glomerular diseases.
Main Methods:
- Diabetic nephropathy was induced in rats and podocytes using high-fat diet, streptozotocin, and hyperlipidemic conditions.
- Apoptosis rates were measured using TUNEL assay.
- Calpain 10 expression and effects were analyzed via real-time PCR, Western blotting, immunofluorescence, and electron microscopy.
Main Results:
- Calpain 10 was significantly upregulated in the kidneys of DN rats and cultured podocytes.
- Elevated Calpain 10 levels correlated with renal dysfunction, tissue damage, and podocyte apoptosis.
- Knockdown of Calpain 10 reduced podocyte apoptosis and increased nephrin expression, indicating podocyte protection.
Conclusions:
- Calpain 10 acts as a pro-apoptotic factor in diabetic nephropathy.
- Targeting Calpain 10 presents a promising therapeutic approach for managing DN and other glomerular diseases.
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