PMID- 33168191 OWN - NLM STAT- MEDLINE DCOM- 20210420 LR - 20240226 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 534 DP - 2021 Jan 1 TI - PGAM1 deficiency ameliorates myocardial infarction remodeling by targeting TGF-beta via the suppression of inflammation, apoptosis and fibrosis. PG - 933-940 LID - S0006-291X(20)31992-6 [pii] LID - 10.1016/j.bbrc.2020.10.070 [doi] AB - Myocardial ischemia-reperfusion (MIR) represents critical challenge for the treatment of acute myocardial infarction diseases. Presently, identifying the molecular basis revealing MIR progression is scientifically essential and may provide effective therapeutic strategies. Phosphoglycerate mutase 1 (PGAM1) is a key aerobic glycolysis enzyme, and exhibits critical role in mediating several biological events, such as energy production and inflammation. However, whether PGAM1 can affect MIR is unknown. Here we showed that PGAM1 levels were increased in murine ischemic hearts. Mice with cardiac knockout of PGAM1 were resistant to MIR-induced heart injury, evidenced by the markedly reduced infarct volume, improved cardiac function and histological alterations in cardiac sections. In addition, inflammatory response, apoptosis and fibrosis in hearts of mice with MIR operation were significantly alleviated by the cardiac deletion of PGAM1. Mechanistically, the activation of nuclear transcription factor kappaB (NF-kappaB), p38, c-Jun NH2-terminal kinase (JNK) and transforming growth factor beta (TGF-beta) signaling pathways were effectively abrogated in MI-operated mice with specific knockout of PGAM1 in hearts. The potential of PGAM1 suppression to inhibit inflammatory response, apoptosis and fibrosis were verified in the isolated cardiomyocytes and fibroblasts treated with oxygen-glucose deprivation reperfusion (OGDR) and TGF-beta, respectively. Importantly, PGAM1 directly interacted with TGF-beta to subsequently mediate inflammation, apoptosis and collagen accumulation, thereby achieving its anti-MIR action. Collectively, these findings demonstrated that PGAM1 was a positive regulator of myocardial infarction remodeling due to its promotional modulation of TGF-beta signaling, indicating that PGAM1 may be a promising therapeutic target for MIR treatment. CI - Copyright (c) 2020. Published by Elsevier Inc. FAU - Wu, Yueheng AU - Wu Y AD - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. Electronic address: enckson@126.com. FAU - Chen, Shaoxian AU - Chen S AD - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. FAU - Wen, Pengju AU - Wen P AD - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. FAU - Wu, Min AU - Wu M AD - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. FAU - Wu, Yijing AU - Wu Y AD - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. FAU - Mai, Mingjie AU - Mai M AD - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. FAU - Huang, Jingsong AU - Huang J AD - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. LA - eng PT - Journal Article DEP - 20201106 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Transforming Growth Factor beta) RN - EC 5.4.2.11 (Phosphoglycerate Mutase) SB - IM MH - Animals MH - Apoptosis MH - Cells, Cultured MH - Fibrosis MH - *Gene Deletion MH - Inflammation/*genetics/metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myocardial Infarction/*genetics/metabolism/pathology MH - Myocardium/metabolism/*pathology MH - Phosphoglycerate Mutase/*genetics/metabolism MH - Rats, Sprague-Dawley MH - Transforming Growth Factor beta/*metabolism MH - Rats OTO - NOTNLM OT - Apoptosis and fibrosis OT - Inflammation OT - Myocardial ischemia-reperfusion OT - PGAM1 OT - TGF-beta EDAT- 2020/11/11 06:00 MHDA- 2021/04/21 06:00 CRDT- 2020/11/10 05:35 PHST- 2020/10/09 00:00 [received] PHST- 2020/10/25 00:00 [accepted] PHST- 2020/11/11 06:00 [pubmed] PHST- 2021/04/21 06:00 [medline] PHST- 2020/11/10 05:35 [entrez] AID - S0006-291X(20)31992-6 [pii] AID - 10.1016/j.bbrc.2020.10.070 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2021 Jan 1;534:933-940. doi: 10.1016/j.bbrc.2020.10.070. Epub 2020 Nov 6.