School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
J Oral Pathol Med. 2019 Feb;48(2):151-158. doi: 10.1111/jop.12805. Epub 2018 Dec 9.
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.
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.
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.
Altogether, these findings suggested that arecoline-increased myofibroblast transdifferentiation was via LINC00974-mediated activation of TGF-β signaling.
口腔黏膜下纤维性变（OSF）是一种进行性的瘢痕性疾病，被认为是口腔的癌前病变。然而，OSF 发病机制的详细分子机制尚不清楚。
在这里，我们检测了一种新型长非编码 RNA LINC00974 在 OSF 中的表达，并研究了其在肌成纤维细胞转分化中的功能作用。通过胶原凝胶收缩、迁移、侵袭和伤口愈合测定等表型分析，评估 LINC00974 过表达或抑制后肌成纤维细胞的活性。
我们发现 LINC00974 在 OSF 组织或肌成纤维细胞中的表达异常上调，并且 LINC00974 与肌成纤维细胞标志物之间存在正相关。我们的结果表明，抑制 LINC00974 抑制了肌成纤维细胞的活性，而 LINC00974 的过表达则增加了肌成纤维细胞的激活。我们证明，在 LINC00974 抑制的肌成纤维细胞中，α-SMA、α-1 型 I 胶原和纤维连接蛋白的表达水平下调。此外，在 LINC00974 抑制的肌成纤维细胞中，TGF-β 的分泌和磷酸化 Smad2 的表达也受到抑制。我们进一步证明，沉默 LINC00974 可防止槟榔碱诱导的肌成纤维细胞激活，而 LINC00974 增加肌成纤维细胞的活性是通过 TGF-β 途径。
总之，这些发现表明，槟榔碱增加肌成纤维细胞的转分化是通过 LINC00974 介导的 TGF-β 信号通路的激活。
