Chih-Yuan Fang1,2, Cheng-Chia Yu3,4,5, Yi-Wen Liao5, Pei-Ling Hsieh6, Ming-Yi Lu4,5, Kuan-Chou Lin2, Ching-Zong Wu1, Lo-Lin Tsai1,2. 1. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan. 2. Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 3. Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. 4. Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. 5. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan. 6. Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan.
Abstract
BACKGROUND: Oral submucous fibrosis (OSF) is a progressive scarring disease and has been considered as a premalignant condition of the oral cavity. However, the detailed molecular mechanisms underlying the pathogenesis of OSF are still unclear. METHOD: Here, we examined the expression of a novel long non-coding RNA LINC00974 in OSF and investigated its function role in myofibroblast transdifferentiation. Phenotypic analyses, including collagen gel contraction, migration, invasion and wound healing assays, were used to assess the myofibroblast activities following overexpression or inhibition of LINC00974. RESULTS: We found that the expression of LINC00974 in OSF tissues or myofibroblasts was aberrantly upregulated, and there was a positive correlation between LINC00974 and myofibroblast markers. Our results showed that inhibition of LINC00974 suppressed the myofibroblast activities, while overexpression of LINC00974 increased the activation. We demonstrated that the expression levels of α-SMA, α-1 type I collagen, fibronectin were downregulated in the LINC00974-inhibited myofibroblasts. Additionally, the TGF-β secretion and phosphorylated Smad2 expression were also repressed in the LINC00974-inhibited myofibroblasts. We further demonstrated that silence of LINC00974 prevented the arecoline-induced myofibroblast activation, and LINC00974-increased myofibroblast activities were via TGF-β pathway. CONCLUSION: Altogether, these findings suggested that arecoline-increased myofibroblast transdifferentiation was via LINC00974-mediated activation of TGF-β signaling.
BACKGROUND: Oral submucous fibrosis (OSF) is a progressive scarring disease and has been considered as a premalignant condition of the oral cavity. However, the detailed molecular mechanisms underlying the pathogenesis of OSF are still unclear. METHOD: Here, we examined the expression of a novel long non-coding RNA LINC00974 in OSF and investigated its function role in myofibroblast transdifferentiation. Phenotypic analyses, including collagen gel contraction, migration, invasion and wound healing assays, were used to assess the myofibroblast activities following overexpression or inhibition of LINC00974. RESULTS: We found that the expression of LINC00974 in OSF tissues or myofibroblasts was aberrantly upregulated, and there was a positive correlation between LINC00974 and myofibroblast markers. Our results showed that inhibition of LINC00974 suppressed the myofibroblast activities, while overexpression of LINC00974 increased the activation. We demonstrated that the expression levels of α-SMA, α-1 type I collagen, fibronectin were downregulated in the LINC00974-inhibited myofibroblasts. Additionally, the TGF-β secretion and phosphorylated Smad2 expression were also repressed in the LINC00974-inhibited myofibroblasts. We further demonstrated that silence of LINC00974 prevented the arecoline-induced myofibroblast activation, and LINC00974-increased myofibroblast activities were via TGF-β pathway. CONCLUSION: Altogether, these findings suggested that arecoline-increased myofibroblast transdifferentiation was via LINC00974-mediated activation of TGF-β signaling.
Authors: Agnieszka H Ludwig-Słomczyńska; Michał T Seweryn; Przemysław Kapusta; Ewelina Pitera; Urszula Mantaj; Katarzyna Cyganek; Paweł Gutaj; Łucja Dobrucka; Ewa Wender-Ożegowska; Maciej T Małecki; Paweł P Wołkow Journal: Mol Med Date: 2021-01-20 Impact factor: 6.354