Abstract
Background/purpose
Oral submucous fibrosis (OSF) is a chronic oral potentially malignant disorder characterized by progressive extracellular matrix deposition, myofibroblast activation, oxidative stress, and inflammatory signaling. However, the upstream microRNA-mediated mechanisms linking fibrogenesis and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activation remain unclear. This study investigated the role of the miR-132/sirtuin 1 (SIRT1) axis in OSF-associated fibrotic and inflammatory responses.
Materials and methods
miR-132 expression was examined in OSF tissues, normal tissues, primary buccal mucosal fibroblasts (BMFs), and fibrotic buccal mucosal fibroblasts (fBMFs) using RNA sequencing and quantitative real-time PCR. Patient-derived fBMFs were transfected with a miR-132 inhibitor or control. Collagen gel contraction, wound healing, intracellular reactive oxygen species (ROS), and inflammasome-related protein expression were assessed. TargetScan prediction, luciferase reporter assays, and western blotting were used to evaluate SIRT1 as a miR-132 target. SIRT1 overexpression was further performed to determine its functional effects.
Results
miR-132 was significantly expressed in fBMFs and its expression positively correlated with alpha-smooth muscle actin (α-SMA) and COL1A1. miR-132 inhibition reduced collagen gel contraction, wound closure, ROS generation, and expression of NLRP3, ASC, cleaved caspase-1, cleaved GSDMD, and cleaved IL-1β. SIRT1 was validated as a direct target of miR-132, as miR-132 inhibition increased SIRT1 protein expression and miR-132 mimic suppressed wild-type SIRT1 3′UTR reporter activity. SIRT1 overexpression reduced α-SMA expression, migration, contraction, and inflammasome marker expression in fBMFs.
Conclusion
miR-132 promotes OSF-related myofibroblast activation, oxidative stress, and NLRP3 inflammasome signaling partly through SIRT1 suppression. Targeting the miR-132/SIRT1 axis may provide a potential strategy for attenuating OSF progression.
Recommended Citation
Chou, Ming-Yung; Ng, Min Yee; Liao, Yi-Wen; Yu, Chuan-Hang; Yu, Cheng-Chia; and Tseng, Sin-Jia
(2026)
"Silencing the miR-132/SIRT1 Axis Suppresses NLRP3 Inflammasome Activation and Myofibroblast Differentiation in Oral Submucous Fibrosis,"
Journal of Dental Sciences: Vol. 21:
Iss.
4, Article 52.
Available at:
https://jds.ads.org.tw/journal/vol21/iss4/52
Publication Date
2026
Received Date
June 18 2026
Accepted Date
July 6 2026
Final Revision Date
July 6 2026
