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LncRNA FAF inhibits fibrosis induced by angiotensinogen II via the TGFβ1-P-Smad2/3 signalling by targeting FGF9 in cardiac fibroblasts
- Source :
- Biochemical and Biophysical Research Communications. 521:814-820
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- The dysregulation of Long noncoding RNAs (lncRNAs) has been implicated in many cardiovascular diseases, including cardiac fibrosis. However, the functions and mechanisms of lncRNAs in cardiac fibroblasts (CFs) have not been fully elucidated. First, we observed a correlation between cardiac remodeling (CR) and lncRNA FAF (FGF9-associated factor, termed FAF) expression in the heart. In vitro, we found that the expression of lncRNA FAF was altered in CFs, whereas it behaved inconsistently in cardiomyocytes (CMs). Next, we investigated the effects of lncRNA FAF on angiotensinogen II (Ang II)-induced cardiac fibrosis in neonatal rat CFs and explored the mechanism underlying these effects. In this study, lncRNA FAF was enriched in CFs and was associated with cardiac fibrosis. Upregulation of lncRNA FAF significantly restrained Ang II-induced increases in cell proliferation, differentiation and collagen accumulation of CFs. Moreover, we found that the function of lncRNA FAF was mainly realized through Transforming growth factor β1 (TGFβ1) secretion and then downregulated phosphorylation of Smad2/3. Additional analysis revealed that Fibroblast growth factor 9 (FGF9) is a direct target of lncRNA FAF, as the overexpression of lncRNA FAF could increase the expression of FGF9 and knockdown of the FGF9 expression could attenuate the down-regulation of lncRNA FAF on TGFβ1-P-Smad2/3 pathway. Furthermore, knockdown of the FGF9 expression also abolished the inhibitory effect of FAF on fibrosis. In summary, we demonstrated that the overexpression of lncRNA FAF could inhibit fibrosis induced by Ang II via the TGFβ1-P-Smad2/3 signalling by targeting FGF9 in CFs.
- Subjects :
- Fibroblast Growth Factor 9
0301 basic medicine
Heart Diseases
Cardiac fibrosis
Biophysics
Smad Proteins
Fibroblast growth factor
Biochemistry
Rats, Sprague-Dawley
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
FGF9
Downregulation and upregulation
Fibrosis
medicine
Animals
Molecular Biology
Cell Proliferation
Gene knockdown
Chemistry
Angiotensin II
Myocardium
Cell Biology
Fibroblasts
medicine.disease
Up-Regulation
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Phosphorylation
RNA, Long Noncoding
Signal Transduction
Transforming growth factor
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 521
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....4e476b322bc859df536209b28ca5112c