Expression of transforming growth factor beta in oral submucous fibrosis

Abstract

Background: Oral submucous fibrosis (OSMF) is a premalignant condition mainly caused by areca nut chewing and is characterized by progressive fibrosis of submucosal tissues and epithelial atrophy. Activation of transforming growth factor beta (TGF-β) signaling is considered main causative event for increased collagen production and fibrosis. In this study, molecular pathogenesis of OSMF was investigated based on the expression of the TGF-β genes in OSMF tissues compared to normal controls. Methods: A total of 33 OSMF and 10 normal tissues were collected from patients and their clinic-epidemiological data was recorded. The expression of TGF-β isoform genes-TGF β1, TGF β2, TGF β3 and its receptor TGF βR1, TGF βR2 was studied by real time polymerase chain reaction (PCR). Comparison of the expression of these genes among normal controls and OSMF patients was done. The PCR results were confirmed by histopathological and immunohistochemical staining. Results: The histological changes included atrophic epithelium, loss of rete ridges, presence of inflammatory cells and dense collagen bundles in connective tissue. PCR showed statistically significant upregulation of TGF-β isoforms in OSMF as compared to normal tissues. Of the three isoforms, maximum fold change was observed in TGF-β1. Similarly, both TGF-βR1 and TGF-βR2 were found to be elevated in OSMF tissues compared to normal. The semi-quantitative analysis by immunohistochemical staining revealed statistically significant difference between normal and OSMF tissues. Conclusion: TGF-β signaling plays a major role in the molecular pathogenesis of OSMF as shown by increased mRNA expression of all the three TGF-β isotypes and their receptors.

Small Molecule “Silmitasertib” Repurposed as Inhibitor of Transforming Growth Factor Beta 1 for the Development of Therapeutics for Oral Submucous Fibrosis

“…In OSMF, aggressive fibrosis of the submucosal tissues increases the risk for development of cancer [2]. Significant upregulation of TGF-β1 has been reported in OSMF [3]. Emerging studies are reflecting exponential increase in OSMF in younger male population [6,23].…”

“…Submucosal fibrosis usually affects oral cavity, pharynx, and esophagus leading to dysphagia and progressive trismus and increases the risk for development of cancer [2]. Activation of transforming growth factor beta (TGF-β) signaling has been reported to lead increased collagen production, and fibrosis and significant upregulation of TGF-β1 have been reported in OSMF as compared to normal tissues [3]. Areca nut chewing has been reported the most probable cause of OSMF [3][4][5].…”

“…Activation of transforming growth factor beta (TGF-β) signaling has been reported to lead increased collagen production, and fibrosis and significant upregulation of TGF-β1 have been reported in OSMF as compared to normal tissues [3]. Areca nut chewing has been reported the most probable cause of OSMF [3][4][5]. Epidemiological evidences reflect exponential increase in OSMF in younger male population [6].…”

Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma

“…TGF–β is upregulated in OSF tissues [ [54] , [55] , [56] ] and its activation is shown by the nuclear localization of p-SMAD2 [ 57 ]. The extracts of areca nut induce TGF-β signaling in epithelial cells with increased levels of p-SMAD2, indicating the induction of TGF-β ligand (TGF-β2) and its activator Thrombospondin1 (THBS-1) leading to activation of TGF-β pathway [ 58 ].…”

The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats

“…The TGF-β family is composed of three subtypes, namely TGF-β1, TGF-β2, and TGF-β3, where TGF-β1 is considered as the major driver of human fibrotic pathologies [ 14 ]. Activation of TGF-β1 signaling has been postulated as the main causative event for increased collagen production in oral submucous fibrosis [ 15 ]. Recently, it has been shown that the expression of TGF-β is increased during fibrosis, and its downstream mediator Smad2/3 is involved in cardiac fibrosis [ 16 ].…”