皮肤桥蛋白通过TGF‑β/NF‑κB通路促进扩张型心肌病的发生发展  

Dermatopontin promotes dilated cardiomyopathy via the TGF‑β/NF‑κB pathway

作　　者：黄霞 任伟[1] 阮永乐[1] 胡锐[1] 石烽 吴智勇[1,2,3] HUANG Xia;REN Wei;RUAN Yongle;HU Rui;SHI Feng;WU Zhiyong(Dept.of Cardiovascular Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China;Hubei Key Laboratory of Cardiology,Wuhan 430060,Hubei,China;Cardiovascular Research Institute,Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院心血管外科,湖北武汉430060 [2]心血管病湖北省重点实验室,湖北武汉430060 [3]武汉大学心血管病研究所,湖北武汉430060

出　　处：《武汉大学学报(医学版)》2025年第1期14-19,47,共7页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:82300539)。

摘　　要：目的:探讨皮肤桥蛋白(DPT)在扩张型心肌病中纤维化和重塑中的作用及其分子机制。方法:选取确诊为扩张型心肌病的患者为扩心病组,另选取健康器官捐献者作为对照组,检测两组心脏DPT表达水平。用阿霉素培养人心脏成纤维细胞(HCFs)以模拟体外心脏损伤,并对HCFs进行DPT敲低及过表达处理,检测HCFs中DPT及TGF-β/NF-κB信号通路相关蛋白TGF-β1、Smad2、NF-κB p65、p-NF-κB p65表达水平。通过CCK-8和细胞划痕实验检测HCFs的增殖和迁移能力。结果:在人体组织中,通过免疫组化染色及Western Blot发现,扩心病组心脏中DPT的表达显著升高(P<0.05)。在细胞实验中,DPT过表达后HCFs中TGF-β1、Smad2、NF-κB p65、p-NF-κB p65的表达显著升高(P<0.05)。此外,过表达DPT可显著提高HCFs的增殖、迁移能力。结论:DPT表达上调可增加TGF-β1、Smad2、NF-κB p65、p-NF-κB p65的表达,可导致心脏成纤维细胞的增殖迁移,与扩张型心肌病的发生、发展密切相关。Objective:To investigate the role of dermatopontin(DPT)in fibrosis and remodeling in dilated cardiomyopathy and its molecular mechanism.Methods:Patients diagnosed with dilated cardiomyopa-thy were selected as the dilated cardiomyopathy group and healthy organ donors were selected as the control group.The expression levels of DPT in hearts were detected.Human cardiac fibroblasts(HCFs)were cultured with doxorubicin(DOX)to model cardiac injury in vitro,then the HCFs were treated after the procedures of DPT knock-down and overexpression,respectively,and the expression levels of DPT,TGF-β/NF-κB signaling pathway proteins TGF-β1,Smad2,NF-κB p65,and p-NF-κB p65 in HCFs were determined.The proliferation and migration ability of HCFs were detected by CCK-8 and the cell scratch test.Results:The expression of DPT in the hearts with dilated heart disease was significantly increased by immunohistochemical staining and Western Blot(P<0.05).In cell experiments,the expressions of TGF-β1,Smad2,NF-κB p65,and p-NF-κB p65 in HCFs in-creased significantly after the increase of DPT expression(P<0.05).In addition,overexpression of DPT can significantly improve the proliferation and migration ability of HCFs.Conclusion:Up-regu-lation of DPT expression can increase the expression of TGF-β1,Smad2,NF-κB p65,and p-NF-κB p65,and lead to the proliferation and migration of cardiac fibroblasts,which is closely related to the occurrence and development of dilated cardiomyopathy.

关 键 词：皮肤桥蛋白 扩张型心肌病 TGF-β/NF-κB信号通路 心脏成纤维细胞 

分 类 号：R654.2[医药卫生—外科学]