PMID- 38451182 OWN - NLM STAT- MEDLINE DCOM- 20240322 LR - 20240329 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 16 IP - 5 DP - 2024 Mar 6 TI - The low expression of miR-155 promotes the expression of SHP2 by inhibiting the activation of the ERK1/2 pathway and improves cell pyroptosis induced by I/R in mice. PG - 4778-4788 LID - 10.18632/aging.205631 [doi] AB - This study aims to explore the specific mechanism by which miR-155 regulates SHP2 expression in mouse ischemia-reperfusion (I/R) induced necroptosis. Various methods including cardiac ultrasound, TTC staining, Masson staining, TUNEL staining, and Western blotting were used to examine changes in the morphology and function of the rat left ventricle, myocardial fibrosis, as well as the expression of proteins related to tissue and cardiomyocyte necroptosis pathways. In vivo results showed that knockdown (KD) of miR-155 significantly improved cardiac ultrasound parameters (EF, FS, LVAW;d, and LVAW;s), reduced the myocardial infarction area, myocardial fibrosis, and cell apoptosis in I/R mice, upregulated cardiac SHP2 protein expression, and other proteins including p-ERK1/2, NLRP3, GSDMD, caspase-3, caspase-4, and caspase-11 were also significantly decreased. In vitro experiments showed that compared with the SHP2 WT miR-155 KD group, SHP2 protein expression was significantly increased in the SHP2 WT miR-155 KD group, while the expression of other proteins was significantly reduced, consistent with in vivo results. MiR-155 can regulate ERK1/2 and NLRP3 through SHP2. After adding the ERK1/2 inhibitor U0126 to cardiomyocytes from SHP2 KO mice, it was found that the expression of proteins other than SHP2 significantly decreased compared to SHP2 KO cells without the inhibitor. In summary, low expression of miR-155 promoted the expression of SHP2 and improved mouse I/R-induced necroptosis by inhibiting the activation of the ERK1/2 pathway. FAU - Liu, Mengru AU - Liu M AD - Department of Integrative Medicine Cardiology, China-Japan Friendship Hospital, Beijing 100029, China. FAU - Fu, Dongliang AU - Fu D AD - Department of Integrative Medicine Cardiology, China-Japan Friendship Hospital, Beijing 100029, China. FAU - Gao, Tong AU - Gao T AD - Department of Cardiology, Beijing Tsinghua Changgung Hospital, Beijing 100029, China. FAU - Jiang, Hong AU - Jiang H AD - Department of Integrative Medicine Cardiology, China-Japan Friendship Hospital, Beijing 100029, China. FAU - Yang, Peng AU - Yang P AD - Department of Integrative Medicine Cardiology, China-Japan Friendship Hospital, Beijing 100029, China. FAU - Li, Xianlun AU - Li X AD - Department of Integrative Medicine Cardiology, China-Japan Friendship Hospital, Beijing 100029, China. LA - eng PT - Journal Article DEP - 20240306 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (MIRN155 microRNA, rat) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - EC 3.1.3.48 (Ptpn11 protein, mouse) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) SB - IM MH - Animals MH - Mice MH - Rats MH - Fibrosis MH - MAP Kinase Signaling System MH - *MicroRNAs/metabolism MH - *Myocardial Infarction/metabolism MH - Myocytes, Cardiac/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Pyroptosis MH - Reperfusion MH - Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism PMC - PMC10968689 OTO - NOTNLM OT - I/R OT - SHP2 OT - miR-155 OT - pyroptosis COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study. EDAT- 2024/03/07 12:43 MHDA- 2024/03/22 06:44 PMCR- 2024/03/15 CRDT- 2024/03/07 09:52 PHST- 2023/06/16 00:00 [received] PHST- 2024/01/26 00:00 [accepted] PHST- 2024/03/22 06:44 [medline] PHST- 2024/03/07 12:43 [pubmed] PHST- 2024/03/07 09:52 [entrez] PHST- 2024/03/15 00:00 [pmc-release] AID - 205631 [pii] AID - 10.18632/aging.205631 [doi] PST - ppublish SO - Aging (Albany NY). 2024 Mar 6;16(5):4778-4788. doi: 10.18632/aging.205631. Epub 2024 Mar 6.