Transforming growth factor-beta 1 and TGF-beta 2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation

Background and objectives: Oral Submucous Fibrosis (OSF) is a potentially malignant oral disorder which leads to fibrosis of the oral mucosa and has a high rate of malignant transformation. The consumption of various forms of areca nut is causatively linked to the condition. The constituents of areca nut activate several pro-fibrotic cytokines, chiefly transforming growth factor-1, 2, which leads to an increased deposition and decreased degradation of extracellular matrix and collagen. TGF-1, 2 probably represent the major pathway in the deposition of collagen fibres in this condition. The present study aims to identify and correlate the expressions of TGF-1 and TGF-2 immunohistochemically on paraffin sections of various stages of OSF. A comparison was also made between normal oral mucosa and scar tissue and OSF to judge the mode, extent and type of expression of TGF 1, 2. Methods: The expression of TGF-1 antibody (8A11, NovusBio, USA) and TGF-2 antibody (TB21, NovusBio, USA) was detected immunohistochemically on paraffin sections of 58 and 70 cases of OSF respectively, 10 cases of normal oral mucosal tissue and 4 cases of scar tissue. A mapping of the positivity of the two cytokines was done using JenOptik camera and ProReg image analysis software. The results were statistically analysed using one way ANOVA and students "t" test. Results: Expression of TGF-1 and TGF-2 was more in OSF as compared with normal oral mucosa, scar/keloid tissue showing highest values. Positivity for both the markers was seen in epithelium, around the blood vessels, in areas of inflammatory infiltrate, fibroblasts and in muscles. TGF-1 expression was higher and more intense than that of TGF-2 in all the cases. TGF-2 was restricted in its expression to submucosal area with minimal involvement of the epithelium and the deeper muscle tissue. Conclusion: TGF-1 is the most prominent cytokine in the fibrotic pathway and TGF-2 plays a contributory role.