1. The association between RGS4 and choline in cardiac fibrosis
- Author
-
Jie Yu, Xiuye Zhao, Jing Guo, Yue Sun, Wen Li, Pengzhou Hang, Zhimin Du, and Ziyi Fan
- Subjects
Male ,medicine.medical_specialty ,Cardiac fibrosis ,MAP Kinase Signaling System ,Myocardial Infarction ,RGS4 ,Smad Proteins ,030204 cardiovascular system & hematology ,Biochemistry ,Choline ,Transforming Growth Factor beta1 ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Western blot ,In vivo ,Fibrosis ,Internal medicine ,TGF-β1 ,medicine ,Animals ,Gene Silencing ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Ejection fraction ,medicine.diagnostic_test ,QH573-671 ,business.industry ,Research ,Myocardium ,Cell Biology ,Fibroblasts ,medicine.disease ,Up-Regulation ,CTGF ,Endocrinology ,chemistry ,Medicine ,Myocardial fibrosis ,business ,Cytology ,RGS Proteins - Abstract
Background Myocardial fibrosis is caused by the adverse and powerful remodeling of the heart secondary to the death of cardiomyocytes after myocardial infarction. Regulators of G protein Signaling (RGS) 4 is involved in cardiac diseases through regulating G protein-coupled receptors (GPCRs). Methods Cardiac fibrosis models were established through cardiac fibroblasts (CFs) treatment with transforming growth factor (TGF)-β1 in vitro and mice subjected to myocardial infarction in vivo. The mRNA expression of RGS4, collagen I/III and α-SMA detected by qRT-PCR. Protein level of RGS4, collagen I, CTGF and α-SMA detected by Western blot. The ejection fraction (EF%) and fractional shortening (FS%) of mice were measured by echocardiography. Collagen deposition of mice was tested by Masson staining. Results The expression of RGS4 increased in CFs treatment with TGF-β1 and in MI mice. The model of cardiac fibrosis detected by qRT-PCR and Western blot. It was demonstrated that inhibition of RGS4 expression improved cardiac fibrosis by transfection with small interfering RNA in CFs and injection with lentivirus shRNA in mice. The protective effect of choline against cardiac fibrosis was counteracted by overexpression of RGS4 in vitro and in vivo. Moreover, choline inhibited the protein level of TGF-β1, p-Smad2/3, p-p38 and p-ERK1/2 in CFs treated with TGF-β1, which were restored by RGS4 overexpression. Conclusion This study demonstrated that RGS4 promoted cardiac fibrosis and attenuated the anti-cardiac fibrosis of choline. RGS4 may weaken anti-cardiac fibrosis of choline through TGF-β1/Smad and MAPK signaling pathways.
- Published
- 2021