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MicroRNA-302c modulates peritoneal dialysis-associated fibrosis by targeting connective tissue growth factor

Xiejia Li1, Hong Liu1, Lin Sun1

  • 1Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China.

Journal of Cellular and Molecular Medicine
|January 30, 2019
PubMed

Insights

MicroRNA-302c (miR-302c) may protect against peritoneal fibrosis in patients undergoing peritoneal dialysis (PD). This study reveals a novel TGF-β1/miR-302c/CTGF pathway involved in PD-related fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Long-term peritoneal dialysis (PD) can induce mesothelial/epithelial-mesenchymal transition (MMT/EMT) and fibrosis, leading to ultrafiltration failure and PD discontinuation.
  • MicroRNA-302c (miR-302c) is implicated in suppressing MMT in cancer, but its role in PD-related MMT remains unclear.

Purpose of the Study:

  • To investigate the role of miR-302c in MMT and fibrosis during PD.
  • To explore the potential therapeutic application of miR-302c in preventing peritoneal fibrosis in PD patients.

Main Methods:

  • Measured miR-302c levels in mesothelial cells from PD patients.
  • Overexpressed miR-302c in a human peritoneal mesothelial cell line (HMrSV5) and mouse peritoneum.
  • Treated cells and peritoneum with TGF-β1 or high glucose peritoneal dialysate.
  • Assessed MMT markers, fibrosis, and connective tissue growth factor (CTGF) expression.

Main Results:

  • MiR-302c levels were measured in PD patient effluents.
  • Overexpression of miR-302c alleviated peritoneal fibrosis in PD mouse models.
  • MiR-302c negatively regulated CTGF expression, reversing TGF-β1-induced upregulation.
  • A novel TGF-β1/miR-302c/CTGF pathway was identified in PD-related MMT and fibrosis.

Conclusions:

  • MiR-302c plays a significant role in regulating MMT and fibrosis during PD through the TGF-β1/miR-302c/CTGF pathway.
  • MiR-302c demonstrates potential as a biomarker for peritoneal fibrosis and a therapeutic target for protecting against fibrosis in PD patients.
Keywords:
connective tissue growth factorfibrosismesothelial-mesenchymal transitionmicroRNA-302cperitoneal dialysis

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