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- W4377011301 abstract "Cardiac ischemia/reperfusion (I/R) injury is a complicated pathological event, which has close association with pyroptosis. This study uncovered the regulatory mechanisms of fat mass and obesity-associated protein (FTO) in NLRP3-mediated pyroptosis during cardiac I/R injury. H9c2 cells were stimulated with oxygen–glucose deprivation/reoxygenation (OGD/R). Cell viability and pyroptosis were detected by CCK-8 and flow cytometry. Western blotting or RT-qPCR was performed to analyze target molecule expression. NLRP3 and Caspase-1 expression was observed by immunofluorescence staining. IL-18 and IL-1β production was detected by ELISA. The total m6A and m6A level of CBL was determined by dot blot assay and methylated RNA immunoprecipitation-qPCR, respectively. The interaction between IGF2BP3 and CBL mRNA was confirmed by RNA pull-down and RIP assays. The protein interaction between CBL and β-catenin and β-catenin ubiquitination were evaluated by Co-IP. Myocardial I/R model was established in rats. We determined infarct size by TTC staining and pathological changes by H&E staining. LDH, CK-MB, LVFS, and LVEF were also assessed. FTO and β-catenin were down-regulated, while CBL was up-regulated by OGD/R stimulation. FTO/β-catenin overexpression or CBL silencing restrained OGD/R-induced NLRP3 inflammasome-mediated pyroptosis. CBL repressed β-catenin expression via ubiquitination and degradation. FTO reduced the mRNA stability of CBL by inhibiting m6A modification. CBL-mediated ubiquitination and degradation of β-catenin were involved in FTO-induced pyroptosis inhibition during myocardial I/R injury. FTO inhibits NLRP3-mediated pyroptosis to attenuate myocardial I/R injury via repressing CBL-induced ubiquitination degradation of β-catenin." @default.
- W4377011301 created "2023-05-19" @default.
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- W4377011301 date "2023-05-18" @default.
- W4377011301 modified "2023-10-03" @default.
- W4377011301 title "<scp>FTO</scp> represses <scp>NLRP3</scp> ‐mediated pyroptosis and alleviates myocardial ischemia–reperfusion injury via inhibiting <scp>CBL</scp> ‐mediated ubiquitination and degradation of β‐catenin" @default.
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- W4377011301 doi "https://doi.org/10.1096/fj.202201793rr" @default.
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