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.
Highlights
Idiopathic pulmonary fibrosis (IPF) a progressive interstitial pneumonia with poor prognosis [1]
We characterized that sirt1 Long noncoding RNAs sirt1 antisense (AS) inhibited transforming growth factor β1 (TGF-β1)-induecd epithelial-mesenchymal transition (EMT) of alveolar epithelial cells in idiopathic pulmonary fibrosis (IPF). sirt1 AS was a negative regulator of EMT and has anti-fibrosis function to alleviate the progression of IPF
The results further revealed that sirt1 AS directly bound sirt1 mRNA to increase the stability of its mRNA, to upregulate sirt1 expression; Sirt1 AS suppressed EMT of alveolar epithelial cells in a sirt1-dependent way
Summary
Idiopathic pulmonary fibrosis (IPF) a progressive interstitial pneumonia with poor prognosis [1]. Emerging evidence suggests that lncRNAs play an important role in the pathogenesis of IPF [7] and a number of lncRNAs have been identified as the regulators of the epithelialmesenchymal transition (EMT) in IPF [8, 9]. EMT is a process in which fully differentiated epithelial cells are transformed into a mesenchymal phenotype, with the loss of epithelial markers (such as E-cadherin), and an increase in cell motility associated protein (such as αSMA), and EMT plays an important role in pulmonary fibrosis [10]. Antisense lncRNAs have been reported to regulate cell proliferation and differentiation [13]. We have previously demonstrated that lncRNA zinc finger E-box binding homeobox 1 (ZEB1) antisense RNA1 could facilitate EMT by regulating miR-141-3p/ZEB1 axis in IPF rats [14]. There is no more information about the function of antisense lncRNAs in IPF
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