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Updated: Jul 8, 2025

Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli
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T-2 Toxin-Mediated β-Arrestin-1 O-GlcNAcylation Exacerbates Glomerular Podocyte Injury via Regulating Histone

Tushuai Li1,2,3, Wenxue Sun4,5,6, Shenglong Zhu2,3

  • 1School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou, 215500, P.R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 12, 2023
PubMed

Insights

T-2 toxin causes kidney damage by affecting podocytes. This study reveals that O-linked N-acetylglucosaminylation (O-GlcNAcylation) of β-arrestin-1 is key, as inhibiting it protects against T-2 toxin-induced podocyte injury.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Epigenetics

Background:

  • T-2 toxin induces renal dysfunction and podocyte damage.
  • Metabolic reprogramming and epigenetic modifications are implicated in podocyte injury.

Purpose of the Study:

  • To investigate the role of O-linked N-acetylglucosaminylation (O-GlcNAcylation) in T-2 toxin-induced podocyte injury.
  • To elucidate the underlying molecular mechanisms involving metabolic and epigenetic changes.

Main Methods:

  • Metabolomics analysis of human podocytes exposed to T-2 toxin.
  • Assessing O-GlcNAcylation, β-arrestin-1, histone acetylation, and autophagy.
  • Utilizing mass spectrometry and co-immunoprecipitation to identify O-GlcNAc targets.
  • Employing mouse and podocyte models to evaluate therapeutic interventions.

Main Results:

  • T-2 toxin upregulates glucose transporter type 1 (GLUT1) and enhances the hexosamine biosynthetic pathway.
  • This leads to increased O-GlcNAcylation of β-arrestin-1, stabilizing it and activating the mTOR pathway.
  • Inhibition of β-arrestin-1 or O-GlcNAc transferase (OGT) ameliorates T-2 toxin-induced renal and podocyte injury.
  • O-GlcNAcylation of β-arrestin-1 suppresses autophagy by promoting H4K16 acetylation.

Conclusions:

  • OGT-mediated β-arrestin-1 O-GlcNAcylation is a critical regulator of T-2 toxin-induced podocyte injury.
  • This process involves mTOR pathway activation and autophagy inhibition.
  • Targeting β-arrestin-1 or OGT presents a potential therapeutic strategy for T-2 toxin-associated glomerular and podocyte injury.
Keywords:
T-2 toxinsglomerular injuryhistone acetylationo-glcnacylationpodocyte injuryβ-arrestin-1

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