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

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

  • Eur J Pharmacol. 2024 Nov 5:982:176931. doi: 10.1016/j.ejphar.2024.176931.
Zhenglin Yi 1,  Peihua Liu 1,  Yinfan Zhang 2,  Dilishati Mamuti 3,  Weimin Zhou 1,  Zhi Liu 1,  Zhi Chen 4
Affiliations

Affiliations

  • 1 Departments of Urology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
  • 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China; Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, China.
  • 3 The Sixth Clinical Medical College Hospital, Xinjiang Medical University, Urumchi, China.
  • 4 Departments of Urology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China. Electronic address: czhi1011@csu.edu.cn.
PMID: 39182553 DOI: 10.1016/j.ejphar.2024.176931
Abstract

Renal fibrosis is among the major factors contributing to the development of chronic kidney disease. In this regard, although N6-methyladenosine (m6A) modification and micro-RNAs (miRNAs) have been established to play key roles in diverse physiological processes and disease/disorder development, further research is required to identify the probable mechanisms and processes associated with their involvement in renal fibrosis. In this study, we show that transforming growth factor β1 (TGF-β1)-induced human proximal tubule epithelial cells (HK2) are characterized by dose-dependently higher methyltransferase-like 3 (METTL3) expression. Furthermore, METTL3 was found to enhance pri-miR-199a-3p maturation and miR-199a-3p expression in an m6A-dependent manner, whereas miR-199a-3p sponges prostate apoptotic response 4 (Par4), thereby regulating its expression. Collectively, our findings in this study indicate that the METTL3/miR-199a-3p/Par4 axis plays a key role in the development of obstructive nephrogenic fibrosis.

Keywords

Obstructive nephropathy; Renal fibrosis; ceRNA; m6A; miRNA.

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