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.
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This work was supported by the National Natural Science Foundation of China (81872871, 82070283, 81530010 and 82073844).
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SJL, YJL, and ZWP designed the research. SJL and MYZ supervised all aspects of the research. XD, XD, SS, WDS, HWX, DYL, and JFZ performed cellular experiments. JXW, WQY, WH, XXH, and QZ conducted animal experiments. SJL, YJL, and ZWP wrote and finalized the manuscript.
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Luo, S., Zhang, M., Wu, H. et al. SAIL: a new conserved anti-fibrotic lncRNA in the heart. Basic Res Cardiol 116, 15 (2021). https://doi.org/10.1007/s00395-021-00854-y
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DOI: https://doi.org/10.1007/s00395-021-00854-y