Senescent Fibroblast in Oral Submucous Fibrosis Aids in Disease Progression and Malignant Transformation.

Abstract

Aim:To study the role of senescent fibroblasts (SFs) and its secretory phenotypes promoting fibrosis and malignancy in oral submucous fibrosis (OSMF).Material Methods:A total of 20 cases of OSMF and 20 normal oral mucosal tissues were taken for the study. The tissue sections were stained for IHC-immunohistochemistry with senescent cell marker p16INK4a. The supernatant solution of the transport medium was studied for leached out senescent associated secretory proteins (SASP): matrix metalloproteinases 9 (MMP9), interleukins 6 (IL6), vascular endothelial growth factor (VEGF). Tissues were studied for malignant transformation with p53 and Ki67. Fibrosis in the OSMF was tested with lysyloxidase (LOX). The Statistical Package for the Social Sciences (SSPS) statistical software was used to analyze the data.Results:IHC staining for p16INK4ashowed positivity in the connective tissue of OSMF cases which was statistically significant. Antibody assay using enzyme-linked immunosorbent assay (ELISA) showed elevated levels of secretoproteins IL6, MMP9, VEGF in OSMF cases. LOX enzyme levels were also significantly increased in OSMF cases. Proliferative markers Ki67 and p53 were positive in IHC staining in the epithelium of OSMF.Conclusion:This study confirms the presence of SF and its secreto phenotypes in OSMF and showed increased LOX expression which is implicated in fibrosis. These findings suggest that SF may contribute to fibrosis in OSMF. The study also confirms the malignant transformation of the overlying epithelium as shown by p53 and Ki67 positivity.