Inhibitory Role of Family with Sequence Similarity 162 Member A in the Fibrotic Phenotypes of Cardiac Fibroblasts
10.11714/jsysu.med.YX20250186
- VernacularTitle:具有序列相似性的家族162成员A抑制心肌成纤维细胞纤维化表型的作用
- Author:
Chuanmeng ZHOU
1
;
Peiying GUAN
2
;
Rushi WU
2
;
Jiening ZHU
3
;
Juntao FANG
4
;
Yupeng LIU
4
;
Xianhong FANG
4
;
Zhixin SHAN
1
Author Information
1. Guangdong Provincial People's Hospital//Guangdong Academy of Medical Sciences// Southern Medical University， Guangzhou 510080，China
2. School of Medicine， South China University of Technology， Guangzhou 510006， China
3. Guangdong Provincial Key Laboratory of Clinical Pharmacology//Guangdong Provincial People's Hospital//Guangdong Academy of Medical Sciences//Southern Medical University， Guangzhou 510080， China
4. Guangdong Cardiovascular Institute// Guangdong Provincial People's Hospital//Guangdong Academy of Medical Sciences//Southern Medical University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
Fam162a;
myocardial fibrosis;
cardiac fibroblast;
mitochondrial function;
oxidative phosphorylation
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(2):238-250
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the expression of family with sequence similarity 162 member A （Fam162a）， a mitochondrial inner membrane protein， in the fibrosis of cardiac fibroblasts and its regulatory role in modulating the fibrotic phenotype of cardiac fibroblasts. MethodsFam162a protein expression was detected in myocardial samples from patients with heart failure （HF） and mice with transverse aortic constriction （TAC）-induced myocardial remodeling. Primary neonatal mouse cardiac fibroblasts （mCFs） were isolated and cultured， and a cell model of angiotensin Ⅱ （Ang Ⅱ）-induced myocardial fibrosis was established to determine Fam162a protein expression. Recombinant adenovirus was used to mediate Fam162a overexpression， while small interfering RNA （si-RNA） was employed for Fam162a knockdown. Western blot was performed to detect the expression of fibrosis-related proteins， including COL1A1， COL3A1， and α-SMA. EdU staining assay was used to evaluate cell proliferation capacity， and scratch assay combined with Transwell assay was conducted to assess cell migration ability. Immunofluorescence assay was applied to measure mitochondrial membrane potential for reflecting mitochondrial dysfunction； reactive oxygen species （ROS） detection was performed to evaluate cellular oxidative stress status； MitoSox assay was used to reflect the degree of mitochondrial oxidative damage； and ATP detection was conducted to assess the overall cellular energy metabolism. ResultsFam162a expression was significantly downregulated in the myocardium of HF patients and TAC mice， and Ang Ⅱ-treated mCFs， accompanied by increased expression of COL1A1， COL3A1， and α-SMA （all P＜0.05）. Adenovirus-mediated overexpression of Fam162a significantly inhibited Ang Ⅱ-induced upregulation of fibrosis-related genes， as well as cell proliferation and migration. Accordingly， silencing Fam162a aggravated the fibrotic phenotypes of mCFs treated with Ang II. Further studies revealed that the inhibitory effect of Fam162a overexpression on Ang Ⅱ-induced fibrotic phenotype was suppressed following the addition of rotenone （a mitochondrial oxidative respiratory chain inhibitor）， which was accompanied by mitochondrial membrane potential depolarization， excessive ROS production， and insufficient ATP generation. ConclusionFam162a exerts its inhibitory effect on the fibrotic phenotype of cardiac fibroblasts by maintaining mitochondrial membrane potential， promoting ATP production， reducing reactive oxygen species （ROS） generation， and suppressing Smad3 signaling activation.
