School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan.
Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
Int J Mol Sci. 2023 Mar 18;24(6):5811. doi: 10.3390/ijms24065811.
Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely unknown. Here, we showed that miR-424 was aberrantly overexpressed in OSF tissues, and then we assessed its functional role in the maintenance of myofibroblast characteristics. Our results demonstrated that the suppression of miR-424 markedly reduced various myofibroblast activities (such as collagen contractility and migration ability) and downregulated the expression of fibrosis markers. Moreover, we showed that miR-424 exerted this pro-fibrosis property via direct binding to TGIF2, an endogenous repressor of the TGF-β signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-β/Smad pathway, leading to enhanced myofibroblast activities. Altogether, our data revealed how miR-424 contributed to myofibroblast transdifferentiation, and targeting the miR-424/TGIF2 axis may be a viable direction for achieving satisfactory results from OSF treatment.
口腔黏膜下纤维性变（OSF）已被认为是一种潜在的恶性疾病，其特征为炎症和胶原沉积。在各种纤维化调节因子中，microRNAs（miRNA）受到了广泛关注，但 miRNA 介导的调节的详细机制在很大程度上仍不清楚。在这里，我们发现 miR-424 在 OSF 组织中异常过表达，然后评估了其在维持成肌纤维细胞特征中的功能作用。我们的结果表明，miR-424 的抑制显著降低了各种成肌纤维细胞的活性（如胶原收缩性和迁移能力），并下调了纤维化标志物的表达。此外，我们表明 miR-424 通过直接结合 TGF-β 信号的内源性抑制剂 TGIF2 发挥这种促纤维化特性。此外，我们的研究结果表明，miR-424 的过表达激活了 TGF-β/Smad 通路，导致成肌纤维细胞活性增强。总之，我们的数据揭示了 miR-424 如何促进成肌纤维细胞的转分化，靶向 miR-424/TGIF2 轴可能是实现 OSF 治疗满意效果的可行方向。
