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[1]陈媛媛 陈亚芬 孙学然 王燕萍 吴丽苹 杨克 刘艳.糖基化终末产物调控糖尿病合并动脉粥样硬化中FSTL1表达的机制研究[J].国际心血管病杂志,2019,01:31-35.
　CHEN Yuanyuan,CHEN Yafen,SUN Xueran,et al.Regulation mechanism of AGEs on FSTL1 expression in diabetes with atherosclerosis[J].International Journal of Cardiovascular Disease,2019,01:31-35.
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糖基化终末产物调控糖尿病合并动脉粥样硬化中FSTL1表达的机制研究(PDF)

《国际心血管病杂志》[ISSN:1006-6977/CN:61-1281/TN]

期数:
2019年01期
页码:
31-35
栏目:
基础研究
出版日期:
2019-02-20

文章信息/Info

Title:
Regulation mechanism of AGEs on FSTL1 expression in diabetes with atherosclerosis
作者:
陈媛媛 陈亚芬 孙学然 王燕萍 吴丽苹 杨克 刘艳
200011 上海交通大学医学院附属第九人民医院心脏科(陈媛媛,刘艳); 200025 上海交通大学医学院附属瑞金医院心血管病研究所(陈亚芬,孙学然,王燕萍,吴丽苹,杨克)
Author(s):
CHEN Yuanyuan1;  CHEN Yafen2;  SUN Xueran2;  WANG Yanping2;  WU Liping2;  YANG Ke2;  LIU Yan11
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011; 2. Institute of Cardiovascular Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, Chin
关键词:
糖尿病;  动脉粥样硬化;  糖基化终末产物;  卵泡抑素样蛋白1;  巨噬细胞
Keywords:
Diabetes;  Atherosclerosis;  Advanced glycation end products;  Follistatin-like protein 1;  Macrophages
分类号:
-
DOI:
10.3969/j.issn.1673-6583.2019.01.008
文献标识码:
-
摘要:
目的:探讨糖基化终末产物(AGEs)参与调控糖尿病动脉粥样硬化中卵泡抑素样蛋白1(FSTL1)表达的分子机制。方法:采用酶联免疫吸附试验(ELISA)检测糖尿病合并动脉粥样硬化患者血清中FSTL1及AGEs的表达水平,分析外周血中AGEs与FSTL1的相关性。构建糖基化终末产物受体(RAGE)基因敲除小鼠(以C57BL/6野生型小鼠为对照),体外培养小鼠原代巨噬细胞。采用Western blot法检测不同浓度的AGEs-BSA刺激巨噬细胞后FSTL1及其基因5'端启动子区域转录因子AP-1和c-Jun的表达情况,以及特异性抗体阻断RAGE后巨噬细胞FSTL1、AP-1和c-Jun的表达变化。结果:糖尿病合并动脉粥样硬化患者外周血中FSTL1与AGEs水平呈正相关(r=0.148,P=0.021)。AGEs-BSA促进巨噬细胞表达FSTL1和核转录因子AP-1及c-Jun。特异性阻断RAGE信号通路后,AGEs-BSA诱导的FSTL1、AP-1及c-Jun的表达水平明显降低。结论:AGEs-RAGE信号通路可通过调控巨噬细胞中转录因子AP-1及c-Jun的表达来调节FSTL1活性,进而参与糖尿病动脉粥样硬化的发生与发展。
Abstract:
Objective:To detect the regulation and mechanism of advanced glycation end products(AGEs)on follistatin-like protein 1(FSTL1)in diabetes with atherosclerosis.Methods:The expression level of FSTL1 in serum of patients with diabetes and atherosclerosis were detected by ELISA. The correlation of AGEs and FSTL1 in serum were analyzed. Receptor of AGEs(RAGE)knockout mice were built to block the RAGE signaling pathway and wild type C57BL/6 mice were served as control. Primary macrophages of RAGE knockout mice were cultured in vitro. Various concentrations of AGEs-BSA were used to stimulate macrophages and the expression of FSTL1, AP-1 and c-Jun were detected by western blot. Then the expression of FSTL1, AP-1 and c-Jun were detected again by western blot after blocking the RAGE signaling pathway.Results:There was a positive correlation between FSTL1 and AGEs in serum of patients with diabetes and atherosclerosis(r=0.148,P=0.021). AGEs-BSA promoted the expression of FSTL1, AP-1 and c-Jun in macrophages. AGEs-BSA-induced expression of FSTL1, AP-1 and c-Jun were declined after blocking the RAGE signaling pathway specifically.Conclusions:AGEs-RAGE signaling pathway may regulate the activity of FSTL1 by controlling the expression of AP-1 and c-Jun in macrophages and then participate in the progression of diabetes with atherosclerosis.

参考文献/References


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备注/Memo

备注/Memo:
基金项目:国家自然科学基金(81770384,81470547)
作者单位:200011 上海交通大学医学院附属第九人民医院心脏科(陈媛媛,刘艳); 200025 上海交通大学医学院附属瑞金医院心血管病研究所(陈亚芬,孙学然,王燕萍,吴丽苹,杨克)
通信作者:刘艳,Email:liuyan_ivy@126.com
更新日期/Last Update: 2019-02-25