PMID- 38083975
OWN - NLM
STAT- MEDLINE
DCOM- 20240219
LR  - 20240219
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 11
IP  - 7
DP  - 2024 Feb
TI  - T-2 Toxin-Mediated beta-Arrestin-1 O-GlcNAcylation Exacerbates Glomerular Podocyte 
      Injury via Regulating Histone Acetylation.
PG  - e2307648
LID - 10.1002/advs.202307648 [doi]
LID - 2307648
AB  - T-2 toxin causes renal dysfunction with proteinuria and glomerular podocyte 
      damage. This work explores the role of metabolic disorder/reprogramming-mediated 
      epigenetic modification in the progression of T-2 toxin-stimulated podocyte 
      injury. A metabolomics experiment is performed to assess metabolic responses to 
      T-2 toxin infection in human podocytes. Roles of protein 
      O-linked-N-acetylglucosaminylation (O-GlcNAcylation) in regulating T-2 
      toxin-stimulated podocyte injury in mouse and podocyte models are assessed. 
      O-GlcNAc target proteins are recognized by mass spectrometry and 
      co-immunoprecipitation experiments. Moreover, histone acetylation and autophagy 
      levels are measured. T-2 toxin infection upregulates glucose transporter type 1 
      (GLUT1) expression and enhances hexosamine biosynthetic pathway in glomerular 
      podocytes, resulting in a significant increase in beta-arrestin-1 O-GlcNAcylation. 
      Decreasing beta-arrestin-1 or O-GlcNAc transferase (OGT) effectively prevents T-2 
      toxin-induced renal dysfunction and podocyte injury. Mechanistically, 
      O-GlcNAcylation of beta-arrestin-1 stabilizes beta-arrestin-1 to activate the mammalian 
      target of rapamycin (mTOR) pathway as well as to inhibit autophagy during 
      podocyte injury by promoting H4K16 acetylation. To sum up, OGT-mediated 
      beta-arrestin-1 O-GlcNAcylation is a vital regulator in the development of T-2 
      toxin-stimulated podocyte injury via activating the mTOR pathway to suppress 
      autophagy. Targeting beta-arrestin-1 or OGT can be a potential therapy for T-2 toxin 
      infection-associated glomerular injury, especially podocyte injury.
CI  - (c) 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Li, Tushuai
AU  - Li T
AD  - School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou, 
      215500, P.R. China.
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi, 214013, P.R. China.
AD  - Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine 
      Research Institute Wuxi Branch, Wuxi, 214013, P.R. China.
FAU - Sun, Wenxue
AU  - Sun W
AD  - Translational Pharmaceutical Laboratory, Jining First People's Hospital, Shandong 
      First Medical University, Jining, 272000, P.R. China.
AD  - Postdoctoral of Shandong University of Traditional Chinese Medicine, Ji'nan, 
      250355, P.R. China.
AD  - Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, 
      272000, P.R. China.
FAU - Zhu, Shenglong
AU  - Zhu S
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi, 214013, P.R. China.
AD  - Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine 
      Research Institute Wuxi Branch, Wuxi, 214013, P.R. China.
FAU - He, Chengsheng
AU  - He C
AD  - School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou, 
      215500, P.R. China.
FAU - Chang, Tong
AU  - Chang T
AD  - School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou, 
      215500, P.R. China.
FAU - Zhang, Jie
AU  - Zhang J
AUID- ORCID: 0000-0002-9184-0587
AD  - School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou, 
      215500, P.R. China.
FAU - Chen, Yongquan
AU  - Chen Y
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi, 214013, P.R. China.
AD  - Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine 
      Research Institute Wuxi Branch, Wuxi, 214013, P.R. China.
LA  - eng
GR  - BK20221091/Natural Science Foundation of Jiangsu Province/
GR  - 2022M711369/General Program of China Postdoctoral Science Foundation/
GR  - SNG201907/Suzhou Science and Technology Council/
GR  - 20KJB330002/Natural Science Research Project of Universities in Jiangsu Province/
GR  - 2021-BS-008/Doctoral Fund of Jining No.1 People's Hospital/
GR  - 202113050502/Projects of medical and health technology development program in 
      Shandong province/
GR  - 2022YXNS118/Key Research and Development Program of Jining Science and 
      Technology/
PT  - Journal Article
DEP - 20231211
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
RN  - 0 (Histones)
RN  - 0 (beta-Arrestin 1)
RN  - I3FL5NM3MO (T-2 Toxin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Animals
MH  - Acetylation
MH  - Histones/metabolism
MH  - *Podocytes/metabolism
MH  - beta-Arrestin 1/metabolism
MH  - *T-2 Toxin/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - *Kidney Diseases/metabolism
MH  - Mammals/metabolism
PMC - PMC10870076
OTO - NOTNLM
OT  - T-2 toxins
OT  - glomerular injury
OT  - histone acetylation
OT  - o-glcnacylation
OT  - podocyte injury
OT  - beta-arrestin-1
COIS- The authors declare no conflict of interest.
EDAT- 2023/12/12 06:42
MHDA- 2024/02/19 06:42
PMCR- 2023/12/11
CRDT- 2023/12/12 02:35
PHST- 2023/11/22 00:00 [revised]
PHST- 2023/10/12 00:00 [received]
PHST- 2024/02/19 06:42 [medline]
PHST- 2023/12/12 06:42 [pubmed]
PHST- 2023/12/12 02:35 [entrez]
PHST- 2023/12/11 00:00 [pmc-release]
AID - ADVS7160 [pii]
AID - 10.1002/advs.202307648 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2024 Feb;11(7):e2307648. doi: 10.1002/advs.202307648. Epub 2023 
      Dec 11.