Fig. 2
From: Oral submucous fibrosis: pathogenesis and therapeutic approaches
The pathogenesis of OSF. The damage of oral epithelial cells through the production of ROS or through the dysfunction of epithelial cells, such as arrested cell cycle and proliferation inhibition work to promote fibrosis. In addition, the injured epithelial cells also promote EMT process by activating EMT-related signaling pathways. The vascular endothelial injury caused by arecoline also leads to the production of ROS, thus promoting EndMT by activating YAP/TAZ and can eventually leads to fibrosis. Infiltrated immune cells secrete cytokines induced by injury, local ischemia, hypoxia, and SASPs, which were derived from fibroblasts in senescence conditions, thus promoting fibrosis. Leukocytes from circulation may be recruited by chemokines to inflamed areas to secrete profibrotic cytokines. Furthermore, secreted mediators such as TGF-β1, PDGF, bFGF cause fibroblasts activation, which produces excessive ECM. Injured endothelial cells also induce autophagy, fibrinolysis system disorder, and abnormal coagulation function, which leads to microvascular occlusion and further accelerates the process of fibrosis
