2. Academic Validation
  3. METTL14 depletion ameliorates ferroptosis in severe acute pancreatitis by increasing the N6-methyladenosine modification of ACSL4 and STA1

METTL14 depletion ameliorates ferroptosis in severe acute pancreatitis by increasing the N6-methyladenosine modification of ACSL4 and STA1

  • Int Immunopharmacol. 2024 Jan 17:128:111495. doi: 10.1016/j.intimp.2024.111495.
Feng Chen 1,  Minghua Su 1,  Dong Han 1,  Yifan Wang 2,  Menglong Song 3
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China.
  • 2 Department of Emergency Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China. Electronic address: [email protected].
  • 3 Emergency Intensive Care Unit, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China. Electronic address: [email protected].
PMID: 38237228 DOI: 10.1016/j.intimp.2024.111495
Abstract

Methyltransferase-like 14 (METTL14) is implicated in the regulation of various inflammatory disorders. However, its function and molecular mechanism in severe acute pancreatitis (SAP) remains unrevealed. Here we reported an increase in METTL14 in the pancreas of SAP mice and cerulein-LPS-treated AR42J cells. METTL14 depletion reversed inflammatory response and Ferroptosis by reducing the expression of SAT1 (spermidine/spermine N1-acetyltransferase 1) and ACSL4 (acyl-CoA synthetase long chain family member 4) in an m6A-dependent manner. IGF2BP2 (Insulin like growth factor 2 mRNA binding protein 2) could recognize m6A-modified SAT1 and ACSL4 mRNA and enhance their stability. Moreover, METTL14 depletion ameliorated pancreatic injury, inflammation, and Ferroptosis induced by SAP. METTL14 overexpression aggravated SAP by promoting Ferroptosis in vivo. Therefore, these results demonstrated that METTL14-induced Ferroptosis promoted the progression of SAP, and targeting METTL14 or Ferroptosis could be a potential strategy for the prevention and treatment of SAP.

Keywords

Ferroptosis; Inflammation; METTL14; Severe acute pancreatitis.

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