METTL14 depletion ameliorates ferroptosis in severe acute pancreatitis by increasing the N6-methyladenosine modification of ACSL4 and STA1
INTERNATIONAL IMMUNOPHARMACOLOGY(2024)
摘要
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 m6Adependent manner. IGF2BP2 (insulin like growth factor 2 mRNA binding protein 2) could recognize m6Amodified 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.
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关键词
Severe acute pancreatitis,Ferroptosis,Inflammation,METTL14
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