Elevated vimentin expression in buccal mucosal fibroblasts by arecoline in vitro as a possible pathogenesis for oral submucous fibrosis

Chang, Yu‐Chao; Tsai, Chien-Chung; Tai, Kuo‐Wei; Yang, Shyh-Hwang; Chou, Ming‐Yung; Lii, Chong‐Kuei

doi:10.1016/s1368-8375(01)00083-5

Cited by 46 publications

(46 citation statements)

References 29 publications

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“…In our study we found the levels of collagenase an enzyme of matrix metalloproteinase, MMP-1, MMP-8 and MMP-13 were significantly decreased in arecoline induced NOMC and cells from OSF patients which clearly indicates the imbalance in increase of collagen deposition and decrease of collagen degradation. Our result was correlative with previously published data by Chang et al [6,7], who showed that arecoline reduced the MMP-2 secretion and increased the TIMP-1 levels resulting in increased deposition of collagen in the extracellular matrix. The mechanism(s) which cause down regulation of the activity of these enzymes in vitro seems rather speculative at present, which needs further research.…”

Section: Discussionsupporting

confidence: 93%

Therapeutic Interventions in Oral Submucous Fibrosis: An Experimental and Clinical Study

Singh

Mohammad

Pant³

et al. 2014

J. Maxillofac. Oral Surg.

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Introduction Oral submucous fibrosis (OSF) is a chronic debilitating disease and premalignant condition of the oral cavity and is a serious public health issue in India and many parts of the world. The treatment is still elusive and empirical because of poorly understood etiopathogenesis, which is believed to be multifactorial including areca nut chewing, ingestion of chillies, genetic and immunologic processes, nutritional deficiencies, and many others. The present investigations was focused to understand the possible therapeutic interventions of anti-OSF agents in arecoline induced experimental in vitro model of OSF and clinical application of these anti-OSF agents in the restoration of various grade of the disease. Materials and Methods The 127 subjects were selected from patients who visited the OPD of Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, K.G. Medical University, Lucknow. Further the subjects were divided in two groups on the basis of clinical examination. Group-1 subjects showed presence of fibrosis bands in the labial and/or buccal mucosa, loss of elasticity, difficulty to open the mouth and had a habit chewing arecanut in some form. Group-2 subjects had no habit of chewing areca-nut, were apparently healthy with no mucosal disorder. The samples were collected and were immediately transported to Indian Institute of Toxicology Research, Lucknow, for isolation and cultivation of primary cultures of mucosal fibroblast cells. Then isolation and cultivation of oral mucosal fibroblast, identification of non-cytotoxic doses of arecoline, real time PCR, immunocytochemistry, cytokine determination in culture cells, western blot analyses, functional activity of collagenase, lysyl oxidase enzyme activity, collagen beads assay, cyclooxygenase (COX-2) expression analysis was done. Results and Conclusions This study, shows that the reduction of phagocytic cells was strongly related to the arecoline levels in fibroblast culture when we exposed arecoline to normal oral mucosal cells (NOMC) and cells from OSF patient. An enhancement of phagocytic cells was observed following the pre exposure of cells to 1 lM dexamethasone, a glucocorticoids, In this study, histologic evidence is presented which supports the finding that COX-2 expression is upregulated in OSF specimens compared to normal oral submucosal cells. Strong immunostaining for COX-2 was detected in arecoline exposed NOMC and cells from OSF patient. Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes. The number of phagocytic cells and phagocytic activity in cultured human oral fibroblasts from OSF site was lower than the fibroblasts from the normal regions of the same person.

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Section: Discussionsupporting

confidence: 93%

Therapeutic Interventions in Oral Submucous Fibrosis: An Experimental and Clinical Study

Singh

Mohammad

Pant³

et al. 2014

J. Maxillofac. Oral Surg.

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“…Areca nut extract is able to activate f EMT marker in OECM1 and FaDu cells [25]. Arecoline, the major alkaloid in areca nut, could induce the expression of EMT-related molecules (vimentin and IL-6) in human buccal mucosal fibroblast [26,27]. A further understanding on the regulatory networks between S100A4-mediated EMT and arecoline-induced invasiveness may update our current knowledge on the development of therapeutic treatments for metastatic OSCC patients in the future.…”

Section: Discussionmentioning

confidence: 98%

Knockdown of S100A4 impairs arecoline-induced invasiveness of oral squamous cell carcinomas

Hu¹,

Lee²,

Yang³

et al. 2015

Oral Oncology

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“…Stromal fibroblasts or endothelial cells or from terminally epithelial differentiated cells that undergo an EMT process to transdifferentiate myofibroblasts. Up-regulation of EMT-related molecules expression, such as plasminogen activator inhibitor-1 (PAI-1)28, insulin-like growth factor-1 (IGF-1)29, NF-κB30, vimentin31, S100A419, or ZEB111, is involved in the pathogenesis of OSF. Recently, our studies have demonstrated that ZEB1, a well-known factor in activation of EMT program, binds to the α-SMA promoter and transdifferentiate fibroblasts into myofibroblasts11.…”

Section: Discussionmentioning

confidence: 99%

Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

Chang

2016

Sci Rep

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Oral submucous fibrosis (OSF), regarded as a precancerous condition, is characterized by juxta-epithelial inflammatory reaction followed by fibro-elastic change in the lamina properia and epithelial atrophy. The pathologic mechanisms of OSF still need to be further clarified. In the study, we investigated the functional expression of SSEA-4, which is a well-known stemness marker, in myofibroblast activity and the clinical significance in OSF tissues. The expression of SSEA-4 in OSF was evaluated by immunohistochemical staining. Functional analysis of SSEA-4 on myofibroblast activity of OSF was achieved by lentiviral silencing ST3GAL2. Immunohisitochemistry demonstrated that SSEA-4 expression was significantly higher expression in areca quid chewing-associated OSF tissues than those of normal oral mucosa tissues. From flow cytometry analysis, arecoline dose-dependently activated SSEA-4 expression in primary human normal buccal mucosal fibroblasts (BMFs). Sorted SSEA-4-positive cells from fibrotic BMFs (fBMFs) have higher colony-forming unit, collagen gel contraction, and α-smooth muscle actin (α-SMA) expression than SSEA-4-negative subset. Knockdown of ST3GAL2 in fBMFs suppressed SSEA-4 expression, collagen contraction, migration, invasiveness, and wound healing capability. Consistently, silencing ST3GAL2 was found to repress arecoline-induced myofibroblast activity in BMFs. The study highlights SSEA-4 as a critical marker for therapeutic intervention to mediate myofibroblast transdifferentiation in areca quid chewing-associated OSF.

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Elevated vimentin expression in buccal mucosal fibroblasts by arecoline in vitro as a possible pathogenesis for oral submucous fibrosis

Cited by 46 publications

References 29 publications

Therapeutic Interventions in Oral Submucous Fibrosis: An Experimental and Clinical Study

Therapeutic Interventions in Oral Submucous Fibrosis: An Experimental and Clinical Study

Knockdown of S100A4 impairs arecoline-induced invasiveness of oral squamous cell carcinomas

Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

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