TET 2 Deficiency Exacerbates Podocyte Injury and Mitophagy Disorder in Diabetic Nephropathy by Regulating M 5 C Methylation of Bcas3

Oct 4, 2025FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Lack of TET2 worsens kidney cell damage and mitochondrial recycling problems in diabetic kidney disease by changing RNA modifications of Bcas3

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Abstract

A marked increase in 5-methylcytidine (m5C) levels was observed in the kidneys of type 2 diabetic mice.

  • Increased m5C levels in diabetic kidneys were associated with reduced expression of the m5C demethylase TET2.
  • Decreased TET2 expression in renal biopsy samples from diabetic nephropathy patients correlated with impaired renal function.
  • Overexpression of TET2 in high glucose-stimulated podocytes enhanced mitophagy and reduced cell injury.
  • Systemic delivery of AAV-TET2 in diabetic mice led to reduced albuminuria and improved kidney histopathology.
  • TET2 influences mitophagy by modulating the m5C methylation of Breast Carcinoma Amplified Sequence 3 (Bcas3), which also promotes mitophagy.

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