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MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis
Ming-Yung Chou1,2, Pei-Ling Hsieh3, Shih-Chi Chao4,5
1School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan.
Abstract:
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.
Insights
MicroRNA-424 (miR-424) promotes oral submucous fibrosis (OSF) by activating TGF-β signaling. Targeting the miR-424/TGIF2 pathway offers a potential therapeutic strategy for OSF treatment.
Area of Science:
- Biomedical research
- Molecular biology
- Oral pathology
Background:
- Oral submucous fibrosis (OSF) is a potentially malignant disorder characterized by inflammation and collagen deposition.
- MicroRNAs (miRNAs) are implicated in fibrogenesis, but their specific roles in OSF remain unclear.
- Understanding miRNA-mediated mechanisms is crucial for developing effective OSF therapies.
Purpose of the Study:
- To investigate the role of miR-424 in the pathogenesis of oral submucous fibrosis (OSF).
- To elucidate the molecular mechanisms by which miR-424 influences myofibroblast characteristics and fibrogenesis in OSF.
- To evaluate the potential of targeting the miR-424/TGIF2 axis as a therapeutic strategy for OSF.
Main Methods:
- Quantitative analysis of miR-424 expression in OSF tissues.
- Assessment of myofibroblast activities, including collagen contractility and migration, following miR-424 modulation.
- Luciferase reporter assays to confirm direct binding of miR-424 to TGIF2.
- Western blot analysis to evaluate the activation of the TGF-β/Smad signaling pathway.
Main Results:
- miR-424 was significantly overexpressed in OSF tissues.
- Suppression of miR-424 reduced myofibroblast activities and fibrosis markers.
- miR-424 directly targets TGIF2, a repressor of TGF-β signaling.
- Overexpression of miR-424 activated the TGF-β/Smad pathway, enhancing myofibroblast functions.
Conclusions:
- miR-424 plays a critical role in promoting myofibroblast transdifferentiation and fibrogenesis in oral submucous fibrosis.
- The miR-424/TGIF2 interaction modulates TGF-β signaling, contributing to OSF pathogenesis.
- Targeting the miR-424/TGIF2 axis presents a promising therapeutic avenue for oral submucous fibrosis.
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