Transcriptional co-activator p300 participates in atrial fibrosis induced by high hydrostatic pressure by regulating TGF-β/Smad3 signaling pathway
10.3969/j.issn.1001-1978.2021.09.010
- Author:
Sheng-Huan YU
1
;
Long ZENG
1
;
Wei WEI
1
;
Sheng-Huan YU
2
;
Long ZENG
2
;
Fang RAO
2
;
Hai-Yin XIAO
2
;
Chun-Yu DENG
2
;
Yu-Mei XUE
2
;
Shu-Lin WU
2
;
Wei WEI
2
Author Information
1. School of Medicine, South China University of Technology
2. Dept of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Medical Research Center, Guangdong Academy of Medical Sciences
- Publication Type:Journal Article
- Keywords:
atrial fibrillation;
atrium;
fibrosis;
high hydrostatic pressure;
p300;
TGF-β/Smad3
- From:
Chinese Pharmacological Bulletin
2021;37(9):1237-1245
- CountryChina
- Language:Chinese
-
Abstract:
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 Alphal chain (Col-lAl/Col-3Al), 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. 0 5) 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.
