Transforming growth factor-β1 and TGF-β2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation

Abstract

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-β1, β2, which leads to an increased deposition and decreased degradation of extracellular matrix and collagen. TGF-β1, β2 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-β1 and TGF-β2 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 β1, β2.Methods:The expression of TGF-β1 antibody (8A11, NovusBio, USA) and TGF-β2 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-β1 and TGF-β2 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-β1 expression was higher and more intense than that of TGF-β2 in all the cases. TGF-β2 was restricted in its expression to submucosal area with minimal involvement of the epithelium and the deeper muscle tissue.Conclusion:TGF-β1 is the most prominent cytokine in the fibrotic pathway and TGF-β2 plays a contributory role.

New Gene Markers for Metabolic Processes and Homeostasis in Porcine Buccal Pouch Mucosa during Cells Long Term-Cultivation—A Primary Culture Approach

“…As shown by authors, members of the TGF-β family of cytokines distinguish CAFs from oral cancer and from normal oral fibroblasts [ 28 ]. In other studies, the researchers investigated the role of TGF-β in the induction of fibrosis in another oral disorder, namely oral submucous fibrosis (OSF) [ 29 , 30 ]. OSF is a potentially malignant condition of the oral cavity, characterized by a generalized submucosal fibrosis [ 31 ].…”

“…Isoforms of TGF-β , β1 and β2 have been defined as a pro-fibrotic growth factors which cause deposition of extracellular matrix (ECM) by increasing the synthesis of matrix protein like collagen and decreasing the degradation by stimulating various inhibitor mechanisms. As detailed by Kamath et al, expression of TGF-β1 and TGF-β2 was increased in OSF as compared to normal oral mucosa [ 29 ]. Additionally, authors have shown the most prominent role of isoform β1 in the fibrotic pathway.…”

Immunoexpression of alpha smooth muscle actin correlates with serum transforming growth factor‐β1 levels in oral submucous fibrosis

“…This also explains the highest TGF-β1 and α-SMA immunoexpression in the submucosa in advanced OSMF grades. 18,19…”

The predictive value of platelet to lymphocyte and neutrophil to lymphocyte ratio in determining urethral stricture after transurethral resection of prostate

“…[20] A profibrotic factor -TGF-β1-has been shown to play a crucial role in the pathophysiology of fibrotic diseases such as pulmonary fibrosis, oral submucosal fibrosis, systemic sclerosis, renal fibrosis and Peyronie's disease. [21][22][23][24] Besides, TGF-β1 was proven to create fibrosis of the urethra in several animal studies. [25,26] These data may indicate a correlation between platelet counts and TGF-β1 levels.…”