Lentivirus-mediated SOCS3 Overexpression Ameliorates Experimental Autoimmune Myocarditis by Downregulating MCP-1 and TGF-β
10.11969/j.issn.1673-548X.2025.05.021
- VernacularTitle:慢病毒介导SOCS3过表达通过下调MCP-1、TGF-β减轻实验性自身免疫性心肌炎
- Author:
Haidong ZHANG
1
;
Xu ZHANG
;
Jian JIN
Author Information
1. 314000 浙江中医药大学嘉兴大学联培基地;314000 嘉兴市第二医院(嘉兴大学附属第二医院)儿科
- Publication Type:Journal Article
- Keywords:
Autoimmune myocarditis;
Suppressors of cytokine signaling 3;
Janus kinase 2/signal transducer and activator of tran-scription 3 pathway;
Monocyte chemoattractant protein-1;
Transforming growth factor-β
- From:
Journal of Medical Research
2025;54(5):110-117
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of lentivirus-mediated overexpression of suppressors of cytokine sig-naling 3(SOCS3)on the heart of rats with experimental autoimmune myocarditis(EAM).Methods Thirty Lewis rats were randomly di-vided into a control group,EAM group and EAM+SOCS3 group.The EAM rat model was established by subcutaneous injection of cardiac myosin.On day 0 of the experiment,the EAM+SOCS3 group was injected with lentivirus overexpressing SOCS3 via the tail vein,and the EAM group was injected with an equal amount of empty vector lentivirus.On day 21 of the experiment,all rats underwent echocardio-graphy to evaluate cardiac function and were then euthanized.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of myocardial tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum cardiac troponin T,creatine kinase-myocardial band,B-type natriuretic peptide,and myocardial interleukin-6,interleukin-1 β and tumor necrosis fac-tor-α.Immunohistochemistry,real-time quantitative PCR(RT-qPCR)and Western blot(WB)were used to detect the expressions of SOCS3,Janus kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-β(TGF-β)in myocardial tissue.Results The myocardial pathological score,serum lev-els of cardiac troponin T,creatine kinase-myocardial band,B-type natriuretic peptide,and myocardial levels of interleukin-6,inter-leukin-1β,and tumor necrosis factor-α in the EAM group were significantly higher than those in the control group(P＜0.05).The cardiac function of the EAM group was significantly lower than that of the control group(P＜0.05).The mRNA and protein expressions of myocardial JAK2,STAT3,MCP-1 and TGF-β in the EAM group were significantly higher than those in the control group(P＜0.05).These indexes in the EAM+SOCS3 group were significantly restored compared with those in the EAM group(P＜0.05).The mRNA and protein expressions of SOCS3 in the myocardial tissue of the EAM+SOCS3 group were significantly higher than those in the EAM group(P＜0.05).Conclusion Overexpression of SOCS3 may ameliorates the inflammatory response of the myocardium in EAM rats and im-prove cardiac function by inhibiting the JAK2/STAT3 signaling pathway and downregulating the expressions of MCP-1 and TGF-β.
