Abstract
Background: The role of fibroblasts and their response to environmental stressors in the pathogenesis of oral lichen planus (OLP) is uncertain. Following endoplasmic reticulum stress (ERS), fibroblasts can differentiate into myofibroblasts and activate unfolded protein response (UPR), to maintain cell metabolism, regulate inflammatory responses and determine cell fate.
Objectives: This in vitro study sought to determine the effect of tunicamycin-induced ERS (T-ERS) on fibroblasts cultured from OLP lesions (OLP-F), in relation to the expression of the key markers of UPR.
Methods: Normal oral fibroblasts (NOMF) and OLP-F cell lines (n = 3 each) were subjected to T-ERS for 12 hours and 24 hours. The expression of UPR markers (GRP78, IRE1, ATF6, and PERK) and SMA (myofibroblastic differentiation marker) were semi-quantitatively determined using immunocytochemistry. Data were analyzed using the Kruskal-Wallis test, with statistical significance set at P < .05.
Results: Without ERS, the expression of IRE1 was significantly lower in OLP-F compared with NOMF. The same trend was seen for GRP78 and ATF6, but it was not statistically significant. With T-ERS, UPR protein levels were generally lower in NOMF, except for PERK. In OLP-F, IRE1 and ATF6 levels were increased at 12 hours but reduced at 24 hours, although not significantly. SMA levels were significantly lower in OLP-F at 24 hours.
Conclusion: The findings indicate that OLP-F and NOMF respond differently to ERS with a trend toward reduction of UPR protein expression. This suggests differential activation of UPR pathways in OLP with implications relating to its pathogenesis. Further correlation with the ex vivo conditions and validation of the gene expression findings are warranted.