中国病理生理杂志2025，Vol.41Issue(12)：2299-2306,8.DOI:10.3969/j.issn.1000-4718.2025.12.002
CEMIP通过激活心脏成纤维细胞加重小鼠心脏重构的作用及机制研究
Role of CEMIP in cardiac fibroblast activation and myocardial fibrosis:evidence from a pressure-overload murine model
摘要
Abstract
AIM:This study aimed to investigate the role and mechanism of cell migration-inducing protein(CEMIP)in cardiac fibroblast activation and remodeling in a pressure overload-induced murine model.METHODS:Twelve mice were randomly divided into sham operation(sham)and transverse aortic constriction(TAC)-induced heart failure groups(n=6).An additional 24 mice were randomized into the following:sham operation with control virus(sham-oeNC),TAC with control virus(TAC-oeNC),sham operation with CEMIP overexpression virus(sham-oeCEMIP),and TAC with CEMIP overexpression virus(TAC-oeCEMIP)groups(n=6).Adeno-associated virus was used to overexpress CEMIP in the myocardium.Cardiac function was assessed using echocardiography,whereas myocardial fibrosis and hyper-trophy were analyzed using Masson and WGA staining.Fibrosis markers[α-smooth muscle actin(α-SMA),collagen I/III,and galectin-3],heart failure markers[atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)],as well as transforming growth factor-β1(TGF-β1)and mothers against decapentaplegic homolog 3(Smad3)expressions were evaluated using Western blot and RT-qPCR.In vitro,primary cardiac fibroblasts were activated by angiotensin II(Ang II),and CEMIP knockdown was performed using an adenovirus to investigate its effects on fibroblast phenotypic transformation.RESULTS:Western blot and immunohistochemistry indicated significantly increased CEMIP protein ex-pression in the left ventricular tissues of the TAC group compared to the sham group(P<0.01),with specific enrichment in cardiac fibroblasts(P<0.01).Echocardiography revealed that CEMIP overexpression aggravated cardiac dysfunction and ventricular dilation(P<0.01).Masson and WGA staining demonstrated significantly increased interstitial collagen deposition and aggravated cardiac remodeling in the TAC-oeCEMIP group compared to the TAC-oeNC group(P<0.01).Additionally,the TAC-oeCEMIP group showed significantly upregulated fibrosis markers(α-SMA,collagen I and III,ga-lectin-3)and heart failure markers(ANP and BNP)(P<0.01).In an Ang II-induced in vitro fibroblast activation model,CEMIP knockdown significantly suppressed α-SMA,TGF-β1,and Smad3 expression and phenotypic transformation(P<0.01).CONCLUSION:CEMIP exacerbated cardiac remodeling in mice by promoting fibroblast activation and extracel-lular matrix deposition,thereby aggravating cardiac remodeling.关键词
细胞迁移诱导蛋白/心脏重构/心力衰竭/成纤维细胞活化/心肌纤维化Key words
cell migration-inducing protein/cardiac remodeling/heart failure/fibroblast activation/myocar-dial fibrosis分类
医药卫生引用本文复制引用
闫慧,张博方,李昀遥,江洪,黄兵..CEMIP通过激活心脏成纤维细胞加重小鼠心脏重构的作用及机制研究[J].中国病理生理杂志,2025,41(12):2299-2306,8.基金项目
湖北省自然科学基金资助项目(No.2021CFB440) （No.2021CFB440）
国家自然科学基金青年项目(No.82100287) （No.82100287）
湖北省自然科学基金青年项目(No.2021CFB110) （No.2021CFB110）
