PMID- 33417962 OWN - NLM STAT- MEDLINE DCOM- 20210305 LR - 20230709 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 268 DP - 2021 Mar 1 TI - The effect of miR-471-3p on macrophage polarization in the development of diabetic cardiomyopathy. PG - 118989 LID - S0024-3205(20)31749-5 [pii] LID - 10.1016/j.lfs.2020.118989 [doi] AB - AIMS: The imbalance of M1/M2 macrophage ratio promotes the occurrence of diabetic cardiomyopathy (DCM), but the precise mechanisms are not fully understood. The aim of this study was to investigate whether miR-471-3p/silent information regulator 1 (SIRT1) pathway is involved in the macrophage polarization during the development of DCM. METHODS: Immunohistochemical staining was used to detect M1 and M2 macrophages infiltration in the heart tissue. Flow cytometry was used to detect the proportion of M1 and M2 macrophages. Expression of miR-471-3p was quantified by real time quantitative-PCR. Transfection of miRNA inhibitor into RAW264.7 cells was performed to investigate the underlying mechanisms. Bioinformatics methods and western blotting were used to explore the target gene of miR-471-3p and further confirmed by dual luciferase reporter assay. KEY FINDINGS: We observed that M1 macrophages infiltration in the heart of tissue in DCM while M2 type was decreased. M1/M2 ratio was increased significantly in bone marrow-derived macrophages (BMDMs) from db/db mice and in RAW264.7 cells treated with advanced glycation end products (AGEs). Meanwhile, miR-471-3p was significantly upregulated in RAW264.7 cells induced by AGEs and inhibition of miR-471-3p could reduce the inflammatory polarization of macrophages. Bioinformatics analysis identified SIRT1 as a target of miR-471-3p. Both dual luciferase reporter assay and western blotting verified that miR-471-3p negatively regulated SIRT1 expression. SIRT1 agonist resveratrol could downregulate the increased proportion of M1 macrophages induced by AGEs. CONCLUSION: Our results indicated that the development of DCM was related to AGEs-induced macrophage polarized to M1 type through a mechanism involving the miR-471-3p/SIRT1 pathway. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Liu, Guangqi AU - Liu G AD - Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China. FAU - Yan, Dan AU - Yan D AD - Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China. FAU - Yang, Liu AU - Yang L AD - Department of Cardiology, Union Hospital, Huazhong University of Science and Technology, China. FAU - Sun, Yunwei AU - Sun Y AD - Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China. FAU - Zhan, Lin AU - Zhan L AD - Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China. FAU - Lu, Lili AU - Lu L AD - Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China. FAU - Jin, Zhigang AU - Jin Z AD - China Resource & WISCO General Hospital, Wuhan University of Science and Technology, Wuhan, China. FAU - Zhang, Chunxiang AU - Zhang C AD - Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China. FAU - Long, Ping AU - Long P AD - China Resource & WISCO General Hospital, Wuhan University of Science and Technology, Wuhan, China. Electronic address: longping02@tkhealthcare.com. FAU - Chen, Jinhua AU - Chen J AD - Department of Pharmacy, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei Province, China. Electronic address: 2694691756@qq.com. FAU - Yuan, Qiong AU - Yuan Q AD - Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China. Electronic address: yuanqiong@wust.edu.cn. LA - eng PT - Journal Article DEP - 20210105 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Glycation End Products, Advanced) RN - 0 (MIRN471 microRNA, mouse) RN - 0 (MicroRNAs) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) SB - IM EIN - Life Sci. 2023 Sep 1;328:121897. PMID: 37423776 MH - Animals MH - Diabetes Mellitus, Experimental/physiopathology MH - Diabetes Mellitus, Type 2/physiopathology MH - Diabetic Cardiomyopathies/*genetics/*pathology MH - Fibrosis MH - Gene Expression Regulation MH - Glycation End Products, Advanced/toxicity MH - Macrophage Activation MH - Macrophages/drug effects/*pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics MH - Myocardium/pathology MH - RAW 264.7 Cells MH - Sirtuin 1/genetics/metabolism OTO - NOTNLM OT - Diabetic cardiomyopathy OT - Macrophage polarization OT - SIRT1 OT - miR-471-3p EDAT- 2021/01/09 06:00 MHDA- 2021/03/06 06:00 CRDT- 2021/01/08 20:12 PHST- 2020/10/20 00:00 [received] PHST- 2020/12/22 00:00 [revised] PHST- 2020/12/30 00:00 [accepted] PHST- 2021/01/09 06:00 [pubmed] PHST- 2021/03/06 06:00 [medline] PHST- 2021/01/08 20:12 [entrez] AID - S0024-3205(20)31749-5 [pii] AID - 10.1016/j.lfs.2020.118989 [doi] PST - ppublish SO - Life Sci. 2021 Mar 1;268:118989. doi: 10.1016/j.lfs.2020.118989. Epub 2021 Jan 5.