摘要
目的探讨转录辅助激活因子p300在高静水压诱导心房纤维化中的作用及可能机制。方法收集窦性心律、房颤、高血压合并房颤3组人左心耳组织,Western blot检测p300及TGF-β/Smad3信号通路蛋白及纤维化因子Ⅰ型/Ⅲ型胶原蛋白α1链(Col-1A1/Col-3A1)、基质金属蛋白酶2/9(MMP-2/9)的表达。以0、20和40 mmHg的静水压培养小鼠心耳成纤维细胞;对40 mmHg压力培养的细胞分别予姜黄素及敲低p300处理,Western blot检测p300及上述纤维化指标表达的变化;CCK-8法检测细胞增殖能力变化。结果房颤组、高血压合并房颤组患者组织和40 mmHg高静水压培养的细胞p300和TGF-β/Smad3信号通路蛋白及纤维化指标表达明显增加(P<0.05),细胞增殖能力增强(P<0.05);而给予姜黄素或敲低p300处理后,可逆转压力诱导的纤维化指标表达增加(P<0.05)同时降低细胞的增殖(P<0.05)。结论转录辅助激活因子p300通过调控TGF-β/Smad3信号通路参与高静水压诱导的心房纤维化。
Aim To investigate the role and potential mechanism of transcriptional co-activator p300 in atrial fibrosis caused by high hydrostatic pressure. Methods The left atrial appendage tissues of humans in three groups of sinus rhythm, atrial fibrillation(AF), hypertension and AF were collected. The expressions of p300 protein and TGF-β/Smad3 signaling pathway and fibrotic factors as type Ⅰ/Ⅲ collagen Alpha1 chain(Col-1 A1/Col-3 A1), matrix metalloproteinase 2/9(MMP-2/9) were tested by Western blot. Mouse atrial appendage fibroblasts were cultured under hydrostatic pressures of 0, 20 and 40 mmHg. The fibroblasts cultured under 40 mmHg pressure were treated with curcumin and p300 interference RNA. Western blot was used to test changes in the expression of p300 and the above fibrosis indicators. CCK-8 method was used to test changes of cell proliferation. Results The expressions of p300 and TGF-β/Smad3 signaling pathway proteins and fibrotic factors in AF group and hypertension combined with AF group were significantly higher than those in sinus rhythm group(P<0.05). 40 mmHg high hydrostatic pressure stimulation in vitro could increase the expression of p300 and fibrotic factors in fibroblasts(P<0.05) and enhance the proliferation ability( P < 0. 05). Both curcumin and p300 interfering RNA could reverse the increased expression of p300 and fibrotic factors( P < 0. 05) and decrease cell proliferation( P < 0. 05) induced by hydrostatic pressure. Conclusions High hydrostatic pressure can induce atrial fibrosis,which involves the participation of p300 in this process by regulating the TGF-β/Smad3 signaling pathway.
作者
余声欢
曾珑
饶芳
肖海茵
邓春玉
薛玉梅
吴书林
魏薇
YU Sheng-huan;ZENG Long;RAO Fang;XIAO Hai-yin;DENG Chun-yu;XUE Yu-mei;WU Shu-lin;WEI Wei(School of Medicine,South China University of Technology,Guangzhou 510006,China;Dept of Cardiology,Guangdong Cardiovascular Institute,Guangdong Provincial People′s Hospital Medical Research Center,Guangdong Academy of Medical Sciences,Guangzhou 510080,China)
出处
《中国药理学通报》
CSCD
北大核心
2021年第9期1237-1245,共9页
Chinese Pharmacological Bulletin
基金
国家自然科学基金青年科学基金项目(No 81900301)
广州市科技计划项目(No 201904010451)。
作者简介
余声欢(1993-),硕士生,研究方向:心房纤维化分子调控机制,E-mail:yushenghuan2020@163.com;通信作者:魏薇(1980-),博士,副主任医师,研究方向:心律失常临床诊疗和基础,E-mail:vvsquare@163.com。
