Sirt1 antisense long non-coding RNA attenuates pulmonary fibrosis through sirt1-mediated epithelial-mesenchymal transition

Abstract

Long noncoding RNAs sirt1 antisense (sirt1 AS) was reported to play crucial roles in the progression of organ fibrosis. However, the roles of sirt1 AS in idiopathic pulmonary fibrosis (IPF) are still unknown. In addition, we have previously demonstrated that astragaloside IV (ASV), a bioactive saponin extract of the Astragalus root, significantly alleviates IPF by inhibiting transforming growth factor β1 (TGF-β1) induced epithelial-mesenchymal transition (EMT). Further investigations into the influence of ASV on lncRNAs expression will be helpful to delineate the complex regulatory networks underlying the biological function of ASV. Here, we found sirt1 AS expression was significantly decreased in BLM-induced pulmonary fibrosis. We further found that sirt1 AS effectively inhibited TGF-β1-meidated EMT in vitro and alleviated the progression of IPF in vivo. Mechanistically, sirt1 AS was validate to enhance the stability of sirt1 and increased sirt1 expression, thereby to inhibit EMT in IPF. Furthermore, we demonstrated that ASV treatment increased sirt1 AS expression and silencing of sirt1 AS impaired anti-fibrosis effects of ASV on IPF. Collectively, sirt1 AS was critical for ASV-mediated inhibition of IPF progression and targeting of sirt1 AS by ASV could be a potential therapeutic approach for IPF.

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

“…This is in stark contrast to our finding. However, research on EMT in pulmonary fibrosis has been still reported in the lots of literatures recently [61][62][63][64][65][66] . There is no conclusion in this field.…”

Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

“…SIRT-AS protects SIRT1 mRNA degradation by inhibiting miR-34a binding to the 3′UTR of SIRT1 ( 162 ). In one study of bleomycin-induced lung fibrosis, SIRT1-AS overexpression inhibited TGF-β-mediated EMT ( 163 ). Despite these data, more studies will be necessary to confirm the roles of ANRIL and SIRT1-AS in COPD and pulmonary fibrosis.…”

Long non‐coding RNA TUG1 participates in LPS‐induced periodontitis by regulating miR‐498/RORA pathway

“…Long non‐coding RNAs (lncRNAs) are a class of non‐coding transcripts that are longer than 200 nucleotides, lacking protein‐coding capacity (Qian, Cai, & Qian, 2020). A large amount of studies have demonstrated that lncRNAs are widely involved in various biologic processes such as epigenetic regulation, cell proliferation, apoptosis, and differentiation (Haemmerle & Gutschner, 2015).…”