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SAIL: a new conserved anti-fibrotic lncRNA in the heart.
- Source :
-
Basic research in cardiology [Basic Res Cardiol] 2021 Mar 06; Vol. 116 (1), pp. 15. Date of Electronic Publication: 2021 Mar 06. - Publication Year :
- 2021
-
Abstract
- Long non-coding RNAs (lncRNAs) account for a large proportion of genomic transcripts and are critical regulators in various cardiac diseases. Though lncRNAs have been reported to participate in the process of diverse cardiac diseases, the contribution of lncRNAs in cardiac fibrosis remains to be fully elucidated. Here, we identified a novel anti-fibrotic lncRNA, SAIL (scaffold attachment factor B interacting lncRNA). SAIL was reduced in cardiac fibrotic tissue and activated cardiac fibroblasts. Gain- and loss-of-function studies showed that knockdown of SAIL promoted proliferation and collagen production of cardiac fibroblasts with or without TGF-β1 (transforming growth factor beta1) treatment, while overexpression of SAIL did the opposite. In mouse cardiac fibrosis induced by myocardial infarction, knockdown of SAIL exacerbated, whereas overexpression of SAIL alleviated cardiac fibrosis. Mechanically, SAIL inhibited the fibrotic process by directly binding with SAFB via 23 conserved nucleotide sequences, which in turn blocked the access of SAFB to RNA pol II (RNA polymerase II) and reduced the transcription of fibrosis-related genes. Intriguingly, the human conserved fragment of SAIL (hSAIL) significantly suppressed the proliferation and collagen production of human cardiac fibroblasts. Our findings demonstrate that SAIL regulates cardiac fibrosis by regulating SAFB-mediated transcription of fibrotic related genes. Both SAIL and SAFB hold the potential to become novel therapeutic targets for cardiac fibrosis.
- Subjects :
- Animals
Cells, Cultured
DNA-Binding Proteins metabolism
Disease Models, Animal
Fibroblasts pathology
Fibrosis
Male
Mice, Inbred C57BL
Myocardial Infarction genetics
Myocardial Infarction pathology
Myocytes, Cardiac pathology
RNA Polymerase II metabolism
RNA, Long Noncoding genetics
RNA-Binding Proteins metabolism
Transcription, Genetic
Mice
Cell Proliferation
Collagen metabolism
Fibroblasts metabolism
Myocardial Infarction metabolism
Myocytes, Cardiac metabolism
RNA, Long Noncoding metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1435-1803
- Volume :
- 116
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Basic research in cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 33675440
- Full Text :
- https://doi.org/10.1007/s00395-021-00854-y