Related Experiment Video

Updated: Jan 18, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

618

WTAP regulates DDX3Y mRNA via m6A modification to promote high glucose-induced podocytes injury and diabetic

Guanxi Li1, Huijuan Zeng1, Guojia Ru1

  • 1The Second Department of Nephrology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

General Physiology and Biophysics
|September 9, 2025
PubMed

Insights

Wilms' tumor 1-associating protein (WTAP) promotes diabetic nephropathy (DN) by stabilizing DDX3Y mRNA through N6-methyladenosine (m6A) modification, leading to podocyte injury and kidney damage.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Nephrology

Background:

  • Diabetic nephropathy (DN) is a severe diabetes complication with significant health and economic impacts.
  • N6-methyladenosine (m6A) modification is a key epigenetic regulator affecting cellular functions and disease development.
  • Wilms' tumor 1-associating protein (WTAP) is a crucial component of the m6A methyltransferase complex.

Purpose of the Study:

  • To investigate the role of WTAP in diabetic nephropathy (DN).
  • To elucidate the molecular mechanism by which WTAP influences DN progression.
  • To explore the potential of targeting the WTAP/DDX3Y axis in DN treatment.

Main Methods:

  • Bioinformatic analysis of differentially expressed genes in DN.
  • Establishment of a high glucose (HG)-induced podocyte model in vitro.
  • Western blot, CCK-8, ELISA, flow cytometry, and TUNEL assays for cellular analysis.
  • MeRIP and xenograft models for validating m6A modification and in vivo effects.

Main Results:

  • WTAP and DDX3Y expression were elevated in DN conditions and HG-induced podocytes.
  • Knockdown of DDX3Y (sh-DDX3Y) alleviated HG-induced podocyte injury.
  • WTAP enhanced DDX3Y mRNA stability through m6A methylation, worsening podocyte dysfunction.
  • WTAP/DDX3Y modulation in diabetic mice led to renal insufficiency and histopathological damage.

Conclusions:

  • WTAP promotes podocyte injury and DN progression via m6A-mediated regulation of DDX3Y stability.
  • The WTAP/DDX3Y pathway represents a potential therapeutic target for diabetic nephropathy.

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