Search

Oral submucous fibrosis (OSF) is a precancerous condition in the oral cavity, which is closely related to the myofibroblast conversion of buccal mucosal fibroblasts (BMFs) after chronic consumption of areca nut. Emerging evidence suggests pyroptosis, a form of programmed cell death that is mediated by inflammasome, is implicated in persistent myofibroblast activation and fibrosis. Besides, numerous studies have demonstrated the effects of non-coding RNAs on pyroptosis and myofibroblast activities. Herein, we aimed to target key long non-coding RNA PVT1 with natural compound, carvacrol, to alleviate pyroptosis and myofibroblast activation in OSF. We first identified PVT1 was downregulated in the carvacrol-treated fBMFs and then demonstrated that myofibroblast features and expression of pyroptosis makers were all reduced in response to carvacrol treatment. Subsequently, we analysed the expression of PVT1 and found that PVT1 was aberrantly upregulated in OSF specimens and positively correlated with several fibrosis markers. After revealing the suppressive effects of carvacrol on myofibroblast characterisitcs and pyroptosis were mediated by repression of PVT1, we then explored the potential mechanisms. Our data showed that PVT1 may serve as a sponge of microRNA(miR)-20a to mitigate the myofibroblast activation and pyroptosis. Altogether, these findings indicated that the anti-fibrosis effects of carvacrol merit consideration and may be due to the attenuation of pyroptosis and myofibroblast activation by targeting the PVT1/miR-20a axis., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oral submucous fibrosis (OSF) is a progressive scarring disease. MicroRNA-200b (miR-200b) has been reported as a tumour suppressor, but its role in the precancerous OSF remains unknown. In this study, we investigated the impact of miR-200b on myofibroblastic differentiation activity. Arecoline is a major areca nut alkaloid and has been employed to induce the elevated myofibroblast activity in human buccal mucosal fibroblasts (BMFs). Treatment of arecoline in BMFs dose-dependently reduced gene expression of miR-200b, which corresponded with the decreased expression of miR-200b in fBMFs. The arecoline-induced myofibroblast activities were abolished by overexpression of miR-200b in BMFs, and the same results were observed in fBMFs. In addition, α-SMA was inhibited by an increase in miR-200b. We further demonstrated that miR-200b-mediated decrease in ZEB2 led to down-regulation of α-SMA, vimentin. Loss of miR-200b resulted in enhanced collagen contraction and migration capabilities, and knockdown of ZEB2 reversed these phenomena. Lastly, we showed the expression of miR-200b was significantly less and ZEB2 was markedly higher in OSF tissues. These results suggested that down-regulation of miR-200b may contribute to the pathogenesis of areca quid-associated OSF through the regulation of ZEB2 and myofibroblast hallmarks., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: The let-7 family of microRNAs has been considered as tumor suppressors in various cancers; however, the role of let-7c in oral squamous cell carcinoma has not been determined yet., Methods: In this study, phenotypical behaviors and the radio/chemoresistance were examined subsequent to overexpression of let-7c. In addition, the expression of let-7c in cancer stem cells (CSCs) was evaluated and the effect of let-7c on stemness characteristics was assessed. Also, luciferase activity assays were performed to test whether interleukin (IL)-8 was a putative target of let-7c., Results: Our results confirmed that the expression of let-7c in CSCs was reduced, while overexpression of let-7c attenuated the oncogenicity. Moreover, ectopic expression of let-7c in CSCs downregulated the stemness hallmarks and the radio/chemoresistance. Expression and secretion of IL-8 in oral CSCs were both reduced following overexpression of let-7c. Besides, the inhibitory effect of let-7c on various stemness phenotypes was reverted by IL-8, indicating that lower expression of let-7c may confer higher cancer stemness through a failure to downregulate IL-8., Conclusion: These findings revealed the significance of let-7c in the contribution of oral cancer stemness and radio/chemoresistance. Targeting let-7c and its downstream IL-8 may be beneficial to prevent cancer recurrence and metastasis of oral squamous cell carcinoma., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: STRO-1 is a mesenchymal cell marker present on all clonogenic stromal precursors. Current evidence has indicated that the pathogenesis of fibrotic changes may be mediated by stemness properties. The aim of this study was to investigate the role of STRO-1 in areca quid chewing-associated oral submucous fibrosis (OSF)., Methods: Thirty OSF specimens and ten normal buccal mucosae were examined by immunohistochemistry. The activity of STRO-1 from fibroblasts cultured from normal buccal mucosa (BMFs) and OSF (OSFFs) were measureed and the effect of arecoline, a major areca nut alkaloid, on STRO-1 in BMFs was evaluated. Compared the activities between sorted STRO-1 + cells and STRO-1 - cells from OSFF were measured by collagen gel contraction, migration, invasion abilities, and the expression of α-smooth muscle actin (α-SMA) and pro-α1 (I) chain of type I collagen., Results: Our results first showed that the expression of STRO-1 was more evident in areca quid chewing-associated OSF than normal buccal mucosa tissues (P < .05). Arecoline dose-dependently activated the level of STRO-1 in BMFs (P < .05). The relative expression of STRO-1 was significantly higher in OSFFs compared with BMFs (P < .05). In addition, the sorted STRO-1 + cells from OSFFs exhibited higher collagen gel contraction, migration, and invasion abilities as well as elevated expression of α-SMA and pro-α1 (I) chain of type I collagen than the negative subset (P < .05)., Conclusion: These findings suggested that the stemness marker STRO-1 may be a crucial factor in the pathogenesis of areca quid chewing-associated OSF., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Environmental cigarette smoke (CS) contains many compounds that are harmful to the respiratory system and lead to chronic lung inflammation and other lung diseases. Exercise training is known to confer protection against diseases with chronic inflammation by reducing inflammatory response in human or experimental animals. In this study, we investigated the preventive effect of exercise training against lung inflammation induced by environmental CS., Methods and Results: In this study, two groups of mice received air exposure with (the exercise group) or without (the control group) exercise training for 8 weeks and another two groups received air exposure for the first 4 weeks and CS exposure for the following 4 weeks with (the exercise+CS group) or without (the CS group) exercise training for 8 weeks. As compared with lung tissues of control and exercise groups, those of the CS group showed significantly increased bronchoalveolar-capillary permeability, inflammatory cell infiltration, epithelial thickening, expression of proliferating cell nuclear antigen, mucin 2, cytokines, chemokines, adhesion molecules and activation of NF-κB. These CS-induced pathophysiologic consequences were largely prevented in the exercise + CS group., Conclusion: Collectively, prior exercise training may protect against lung inflammation induced by environmental CS in mice by attenuating the activation of NF-κB and the production of inflammatory mediators., (© 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.)