Modified Citrus Pectin Alleviates Diabetic Kidney Disease by Suppressing Pyroptosis in Renal Tubular Epithelial Cells

Qi Wu1, Yubo Guan2, Yijing Li3

  • 1Department of Physiology, School of the Basic Medicine, Xuzhou Medical University, Xuzhou, China.

PubMed

Insights

Modified citrus pectin (MCP) can protect against diabetic kidney disease (DKD) progression by reducing kidney damage and inhibiting cell death. This study clarifies MCP

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Diabetic kidney disease (DKD) is a major complication of diabetes, characterized by persistent oxidative stress and renal tubular epithelial cell injury.
  • Modified citrus pectin (MCP) possesses antioxidant properties, but its specific role and mechanisms in DKD progression are not fully understood.

Purpose of the Study:

  • To investigate the protective effects of MCP on renal tubular epithelial cells in DKD.
  • To elucidate the underlying molecular mechanisms by which MCP regulates cell injury and pyroptosis in DKD.

Main Methods:

  • In vivo studies utilized C57BL/6J and db/db mice to assess MCP's efficacy.
  • In vitro experiments employed normal rat renal tubular epithelial cells (NRK-52E) and Connexin 43 (Cx43+/-) NRK-52E cells to explore mechanisms.
  • Key indicators measured included serum creatinine, urine protein, renal interstitial damage, reactive oxygen species (ROS), P-extracellular signal-regulated kinase (P-ERK), Gasdermin D-NT (GSDMD-NT), thioredoxin-interacting protein (Txnip), thioredoxin 1 (Trx1), and Cx43.

Main Results:

  • MCP treatment ameliorated kidney damage markers (serum creatinine, urine protein) and renal interstitial damage in db/db mice.
  • MCP inhibited the expression of P-ERK and GSDMD-NT in renal tissue.
  • In vitro, MCP improved ROS levels and modulated the expression of P-ERK, Txnip, Trx1, and Cx43, thereby inhibiting pyroptosis via the Cx43-ERK1/2 signaling pathway.

Conclusions:

  • Modified citrus pectin demonstrates significant renoprotective effects in diabetic kidney disease.
  • MCP mitigates renal tubular epithelial cell pyroptosis through the Cx43-ERK1/2 signaling pathway, highlighting its therapeutic potential for DKD.