Osthole mitigates the myofibroblast properties in oral submucous fibrosis by suppressing the TGF-β/smad2 signaling pathway and NCK-AS1 expression

Abstract

Background/purposeNatural products are gaining increasing recognition as an alternative source for alleviating fibrosis as they can regulate various mediators or pathways against fibrosis by targeting non-coding RNAs. In the current study, we aimed to investigate the therapeutic effects of osthole in oral submucous fibrosis (OSF), a precancerous condition of the oral cavity. Materials and methodsThe cytotoxicity of osthole to normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues was assessed using MTT assay. Collagen gel contraction and transwell migration assays were conducted to examine the myofibroblast activities. Besides, the expression of TGF-β/Smad2 signaling as well as α-SMA and type I collagen were measured. Additionally, RNA sequencing was used to identify a potential target involved in the anti-fibrotic effect of osthole. ResultsOsthole exhibited a higher cytotoxic effect on fBMFs compared to normal BMFs and dose-dependently reduced several myofibroblast activities, including collagen gel contractility and transwell migration ability. In addition, the expression of the TGF-β/Smad2 pathway was inhibited along with a lower expression of α-SMA and type I collagen in osthole-receiving cells. Moreover, the administration of osthole downregulated the expression of NCK1-AS1 in fBMFs, which was proven to mediate the anti-fibrosis property of osthole. ConclusionOur results indicate that osthole may be a promising compound to inhibit the progression of OSF.