SAIL: a new conserved anti-fibrotic lncRNA in the heart
| Autor: | Jiaxu Wu, Jifan Zhang, Qi Zhang, Hongwen Xiao, Xin Ding, Wendi Shang, Hao Wu, Wanqi Yang, Xue Dong, Xiaoxi Hu, Zhenwei Pan, Shenjian Luo, Yanjie Lu, Danyang Li, Shuang Su, Mingyu Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Transcription Genetic Physiology Cardiac fibrosis Myocardial Infarction RNA polymerase II RNA-Seq 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Transcription (biology) Physiology (medical) medicine Animals Myocytes Cardiac Gene Cells Cultured Cell Proliferation Gene knockdown biology Scaffold attachment factor B RNA-Binding Proteins Fibroblasts medicine.disease Fibrosis Cell biology DNA-Binding Proteins Mice Inbred C57BL Disease Models Animal 030104 developmental biology cardiovascular system biology.protein RNA Long Noncoding Collagen RNA Polymerase II Cardiology and Cardiovascular Medicine Transforming growth factor |
| Zdroj: | Basic research in cardiology. 116(1) |
| ISSN: | 1435-1803 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink