Transforming growth factor beta 1 in oral submucous fibrosis: An immunohistochemical study - Understanding the pathogenesis

Abstract

Background:The development of fibrosis is pathognomic in the potentially malignant oral disorder, oral submucous fibrosis (OSF). Strong evidence exists to implicate the chewing of areca nut in the pathogenesis of the lesion. The constituents of areca nut activate several pro-fibrotic cytokines, chiefly transforming growth factor beta 1 (TGF-β1), which leads to an increased deposition and decreased degradation of extracellular matrix and collagen. TGF-β1 probably represents the major pathway in the deposition of collagen fibers in this condition. The present study aims to identify and correlate the expressions of TGF-β1 immunohistochemically on paraffin sections of various stages of OSF. Materials and Methods: The expression of TGF-β1 antibody was detected immunohistochemically using the anti-TGF-β1 mouse monoclonal antibodies (8A11-NovusBio USA) on paraffin sections of 58 cases of OSF, 10 cases of normal buccal mucosa tissue and 5 cases of scar tissue. The site, extent, and intensity of expression and quantification of TGF-β1 were noted and a comparative evaluation between various grades of OSF. Scar tissue and normal oral mucosa was made using image analysis software (Jenoptik optical system-ProReg ® Capture Pro 2.8.8 software [2011]). Results: Cells of spinous layer of the epithelium showed more intense staining in all grades of OSF, Grade II showed the highest percentage of expression, same as that of keloid (17%) but less than that of normal mucosa (12%). Positive staining was seen around blood vessels, muscles, fibers in the submucosa and perimuscle fibers. Highest expression was in the muscle in Grade III (80%) compared with normal oral mucosa (37%). Conclusion: These results suggest that the pathogenesis of OSF and scar/keloid could be linked through the TGF-β1 pathway. Interventions directed at the TGF-beta pathway may hold the key in the future management of this oral potentially malignant condition.

Leaving no stone unturned

“…This suggested that the fibrotic change in OSMF may be a reparative process in response to the injury by the noxious agents in areca nut, and thus, targeting this molecule may help in controlling the progression of the disease. [ 13 ] Pant et al . showed in their study that Maria et al .…”

Assessment of fibrosis induced by Bleomycin in a rat model that resembles Oral Submucous Fibrosis

“…Moreover, it was concluded that the pathogenesis of OSF is linked to TGF-β1 pathway which is the main initiator of collagen production. 1,7 Transforming growth factor beta signaling pathway is initiated by attachment of ligand to transmembranous serine/threonine kinase Type I and II receptors, which in turn activates the cascade of SMAD signal transduction pathway. 31,32 In addition, a number of collagen gene promoters which were induced by TGF-β1and dependent upon SMAD-3 have been demonstrated in human dermal fibroblasts.…”

“…5 This led to rigidity of the oral mucosa causing limitation of opening the mouth and difficulty in eating or maintaining oral health. 6 The pathogenesis of the disease is still not confirmed yet and the disease is thought to be a multifactorial condition 7 ; where chewing of betel quid/areca nut has been found as one of the most significant risk factors for OSF. 8 It has been found that Arecoline (alkaloid component of the betel quid) played an important role in the pathogenesis of OSF as it increased the synthesis of collagen.…”

“…9 Transforming growth factor-beta1 (TGF-β1) is a cytokine that has a key role in inducing myofibroblastic phenotype and the regulation of the extracellular matrix assembly and its expression is increased under numerous fibrotic conditions. 7 SMAD proteins are specific mediators of TGF-β signaling pathway that is initiated by attachment of ligand to transmembranous serine/threonine kinase Type I and II receptors, which activates the cascade of SMAD signal transduction pathway. 10,11 It has been reported that fibrosis in scars occurred due to the upregulation of SMAD-3 and downregulation of SMAD-7 through the TGF-β1pathway.…”

Oral Submucosal Fibrosis: A Potentially Malignant Condition to be Considered

“…According to epidemiological data, chewing betel nuts is also most significant risk factors for OSMF. 19 In China, 62.3% of OSMF patients consume betel nuts. Smoking, tobacco chewing, and alcohol consumption, all have been linked to an increased risk of OSMF.…”