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Project description:Background: Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. Methods: A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. Results: A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19+MIF+ epithelial cells and via epithelial-stromal crosstalk. Conclusions: Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.
2024-05-17 | GSE262446 | GEO
Project description:Oral submucous fibrosis (OSF) as one of the malignant disorders endures a series of histopathological stages to invasive oral squamous cell carcinoma (OSCC) eventually. The role of long non-coding RNA (lncRNA) expression in OSF malignant progression is still poorly understood. Genome-wide lncRNA expression profiling of normal mucous, OSF and OSCC tissues was performed by RNA sequencing. Bioinformatic methods were applied for differential lncRNA analysis and functional enrichment analysis. Quantitative-RT-PCR was used to verify identified lncRNAs.21 novel transcripts were differentially expressed among all three stages during OSF progression with varied expression levels. Our study firstly comprehensively elucidated lncRNAs expression profile of the process of OSCC premalignant lesion to OSCC.
2019-02-13 | GSE125866 | GEO
Project description:ABSTRACT: Background: Oral Submucous Fibrosis (OSF) is a chronic inflammatory disease resulting in progressive fibrosis of the oral soft tissues. Habit of chewing betel quid has been proposed as an important etiological factor in the development of this disease. But the exact mechanism of pathogenesis is still not clear. Methods: We took microarray approach to identify differentially regulated genes in 10 OSF tissues against 8 pooled normal tissues using oligonucleotide arrays. Microarray results have been confirmed by qRT-PCR. Regulation of genes in epithelial and fibroblast cells was studied after treatment with arecoline, TGF-b and LAP followed by qRT-PCR. Results: Total number of genes found to be commonly regulated in OSF (p<=0.05 and Fold change>=1.5) tissues are 5288 and among them 2884 are up-regulated and 2404 are down-regulated. Extra cellular matrix genes that have been reported in OSF such as collagens, fibronectin and cytokines ET1, CTGF and TGF-b1 are among the up regulated genes. The list of up and down regulated genes also includes RARRES1, TGM2, THBS1, CHGB, MMP3, SPP1 and ALOX12, C4orf7 respectively. Analysis of microarray data revealed TGF-? pathway as a principal gene network involved in the development of OSF. Intriguingly, there was no regulation of CTGF and THBS1 in fibroblasts by arecoline. However, TGF-b1 treatment regulated all these genes in both epithelial and fibroblast cells. Conclusion: We demonstrate over expression of novel genes in OSF and suggest that OSF development involves TGF-b pathway in an epithelial-stromal cooperation. Targeting TGF-b signaling could be an alternate strategy to treat OSF. Two-condition experiment: 10 OSF tissues against 8 pooled normal tissues
2010-07-30 | E-GEOD-20170 | biostudies-arrayexpress
Project description:Novel epigenetically dysregulated genes in Oral Submucous Fibrosis
| PRJNA658648 | ENA
Project description:ABSTRACT: Background: Oral Submucous Fibrosis (OSF) is a chronic inflammatory disease resulting in progressive fibrosis of the oral soft tissues. Habit of chewing betel quid has been proposed as an important etiological factor in the development of this disease. But the exact mechanism of pathogenesis is still not clear. Methods: We took microarray approach to identify differentially regulated genes in 10 OSF tissues against 8 pooled normal tissues using oligonucleotide arrays. Microarray results have been confirmed by qRT-PCR. Regulation of genes in epithelial and fibroblast cells was studied after treatment with arecoline, TGF-b and LAP followed by qRT-PCR. Results: Total number of genes found to be commonly regulated in OSF (p<=0.05 and Fold change>=1.5) tissues are 5288 and among them 2884 are up-regulated and 2404 are down-regulated. Extra cellular matrix genes that have been reported in OSF such as collagens, fibronectin and cytokines ET1, CTGF and TGF-b1 are among the up regulated genes. The list of up and down regulated genes also includes RARRES1, TGM2, THBS1, CHGB, MMP3, SPP1 and ALOX12, C4orf7 respectively. Analysis of microarray data revealed TGF-? pathway as a principal gene network involved in the development of OSF. Intriguingly, there was no regulation of CTGF and THBS1 in fibroblasts by arecoline. However, TGF-b1 treatment regulated all these genes in both epithelial and fibroblast cells. Conclusion: We demonstrate over expression of novel genes in OSF and suggest that OSF development involves TGF-b pathway in an epithelial-stromal cooperation. Targeting TGF-b signaling could be an alternate strategy to treat OSF.
2010-06-30 | GSE20170 | GEO
Project description:To understand the role of areca nut constituents in manifestation of Oral submucous fibrosis, we studied gene expression profile in epithelial cells following areca nut water extract treatment. A comaprison with TGF-beta induced gene expression changes were performed as epithelial cells were predicted to be source of TGF-beta.
2013-05-22 | GSE38227 | GEO
Project description:To understand the role of areca nut constituents in manifestation of Oral submucous fibrosis, we studied gene expression profile in epithelial cells following areca nut water extract treatment. A comaprison with TGF-beta induced gene expression changes were performed as epithelial cells were predicted to be source of TGF-beta. Control Vs Areca nut 5 ug/ml water extract (5H) (2), Contro Vs TGF-beta (2), Control Vs ALK5 (TbetaRI inhibitor) (2), Control Vs 5H + ALK5 inhibitor (2). (2)- Biological duplicates.
2013-05-22 | E-GEOD-38227 | biostudies-arrayexpress
Project description:To understand the role of areca nut and TGF-β induced gene expression changes in fibroblasts and its contibution in the manifestation of Oral submucous fibrosis, we studied gene expression profile in primary human gingival fibroblast (hGF) cells following treatment with areca nut, TGF-β and both together.
2015-07-06 | GSE59414 | GEO
Project description:Analysis of various of up-regulated and down-regulated genes in normal oral mucosa and different stages of OSF. The report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of oral mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Microarray based study of global gene expression is often used to extract molecular signatures underlying cancer progression. Such endeavors endorse self organizing map, a type of artificial neural network to analyze high dimensional pre-processed transcriptome data to segregate hotspot genes in component plane for disease subtypes. This report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of oral mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Four exclusive cluster patterns, each involving 100 − 300 genes, were identified from component planes for oral study groups. Gene expression associated with each pattern belonged to 32 biological processes. The transcription and RNA processing, and angiogenesis were dominant in normal oral condition, while immunity, cellular differentiation and migration, neuron signalling, connective tissue organization, tumor suppression, and enzyme regulation showed predominance in oral squamous cell carcinoma. In dysplasia skeletal and ligament development processes were dominant while in non-dysplastic sub-mucous fibrosis cytoskeleton reorganization and neuron signalling were pre-dominant. In dysplasia an intermediate pattern with nine different dominant functional processes was identified. This analysis demonstrated utility of self organizing map to capture dominant enriched patterns as visual plots and revealed six common biological processes like transcription and RNA processing, cytoskeleton reorganization, angiogenesis, immunity, neuron signalling, and connective tissue remodeling in the pathogenesis of oral cancer. In fact it could provide an intuitive understanding of molecular course in carcinogenesis and may contribute for combinatorial biomarker discovery.
2016-01-31 | GSE64216 | GEO
Project description:In Asia, oral cancer (OC) and oral submucous fibrosis (OSF) constitute major health problems linked to use of betel quid. This work performed CGH genome-wide analysis of OC (12 from India, 12 from Sri Lanka) and OSF (6 from India) cases with normal controls.
2011-11-30 | E-MTAB-819 | biostudies-arrayexpress