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METTL3 aggravates renal fibrogenesis in obstructive nephropathy via the miR-199a-3p/PAR4 axis

Zhenglin Yi1, Peihua Liu1, Yinfan Zhang2

  • 1Departments of Urology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.

European Journal of Pharmacology
|August 25, 2024
PubMed

Insights

The methyltransferase-like 3 (METTL3) enzyme promotes renal fibrosis by regulating miR-199a-3p and prostate apoptotic response 4 (Par4) expression. This METTL3/miR-199a-3p/Par4 pathway is crucial in obstructive nephrogenic fibrosis development.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Renal Pathophysiology

Background:

  • Renal fibrosis is a key driver of chronic kidney disease.
  • N6-methyladenosine (m6A) modification and micro-RNAs (miRNAs) are implicated in disease development.
  • The specific roles of m6A and miRNAs in renal fibrosis require further elucidation.

Purpose of the Study:

  • To investigate the role of the METTL3/miR-199a-3p/Par4 axis in obstructive nephrogenic fibrosis.
  • To understand the regulatory mechanisms of m6A modification in renal fibrosis.

Main Methods:

  • Utilized transforming growth factor β1 (TGF-β1)-induced human proximal tubule epithelial cells (HK2).
  • Assessed methyltransferase-like 3 (METTL3) expression.
  • Analyzed pri-miR-199a-3p maturation and miR-199a-3p expression in an m6A-dependent manner.
  • Investigated the interaction between miR-199a-3p and prostate apoptotic response 4 (Par4).

Main Results:

  • TGF-β1 induction led to a dose-dependent increase in METTL3 expression in HK2 cells.
  • METTL3 enhanced pri-miR-199a-3p maturation and miR-199a-3p expression via m6A modification.
  • miR-199a-3p was found to sponge and regulate the expression of Par4.

Conclusions:

  • The METTL3/miR-199a-3p/Par4 axis is a critical regulator in the development of obstructive nephrogenic fibrosis.
  • This study elucidates a novel molecular mechanism involving m6A modification in renal fibrosis.
Keywords:
Obstructive nephropathyRenal fibrosisceRNAm6AmiRNA

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