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.

Abstract

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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