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On-line Access: 2022-12-15
Received: 2022-06-27
Revision Accepted: 2022-08-17
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Jun LI, Limin LUO, Yonggang ZHANG, Xiao DONG, Shuyi DANG, Xiaogang GUO, Wenhui DING. Globular adiponectin-mediated vascular remodeling by affecting the secretion of adventitial-derived tumor necrosis factor-α induced by urotensin II[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200346 @article{title="Globular adiponectin-mediated vascular remodeling by affecting the secretion of adventitial-derived tumor necrosis factor-α induced by urotensin II", %0 Journal Article TY - JOUR
球型脂联素对尾加压素II诱导血管外膜分泌肿瘤坏死因子介导血管重构的影响1浙江大学医学院附属第一医院心内科,浙江杭州,310003 2湖北医药学院附属太和医院心内科,湖北十堰,442000 3北京大学第一医院心内科,北京,100034 4浙江大学医学院附属第一医院皮肤科,浙江杭州,310003 5汕头大学医学院附属第二医院心内科,广东汕头,515041 背景:血管外膜炎症在血管重构的发生发展过程中起着非常重要的作用。已有众多研究提示尾加压素II(UII)和脂联素(APN)在调节细胞免疫、代谢、炎症和凋亡方面具有作用。然而,关于它们对血管外膜重构的重要指示因子α-平滑肌肌动蛋白(α-SMA)和肿瘤坏死因子α(TNF-α)表达的影响所知有限。 目的:探索APN如何介导UII诱导的血管外膜分泌TNF-α和α-SMA及其信号转导通路机制。 方法:在体外实验中,将原代培养的大鼠血管外膜成纤维细胞(AFs)和血管外膜组织,用UII、APN和各种信号通路阻断剂孵育1~24小时。收集细胞和组织,分别采用RT-PCR和ELISA检测TNF-α及其受体mRNA和蛋白表达。采用RT-PCR、qPCR、免疫组化、CCK-8等检测APN及其受体(adipoR)的表达。然后通过qPCR和免疫荧光染色(IF)检测TNF-α和α-SMA蛋白和mRNA表达水平。采用RNA干扰(RNAi)研究adipoR基因的功能。应用western blotting观察AMPK磷酸化情况来研究信号通路。在体内实验中,建立APN基因敲除小鼠颈动脉外膜炎症模型,应用qPCR和IF检测TNF-α和α-SMA的表达。 结果:在细胞和组织中,UII通过Rho/PKC途径以剂量和时间依赖性的方式促进TNF-α及其受体的表达。adipoR1、T-cadherin和calreticulin在AFs中高表达,adipoR2低表达,没有观察到APN在AFs中表达。gAd与UII通过adipoR1/T-cadherin/calreticulin/AMPK途径协同而非抑制AFs中α-SMA和TNF-α的表达。同时,gAd和UII能够协同诱导AMPK磷酸化。在APN基因敲除小鼠构建的颈动脉外膜炎症模型中,APN的缺失可上调α-SMA、UII受体(UT)和UII的表达,而抑制TNF-α的表达。 结论:根据我们的研究结果,可以推测UII通过Rho和PKC信号转导通路诱导AFs和大鼠血管外膜中TNF-α及其受体的分泌。APN在血管外膜炎症性疾病的发生发展过程中扮演了重要角色,并可能成为心血管疾病治疗的新靶点。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
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