TGF-β1 Directs TFAM-Mediated Mitochondrial Reprogramming in Oral Submucous Fibrosis

< 0.05) metabolic profile and reduced OPA1 expression. In contrast, TGF-β1 treatments demonstrated mitochondrial fusion, accompanied by increased OPA1 expression. Combined treatments with arecoline and TGF-β1 demonstrated improved cell survival, reduced fission, and improved mitochondrial bioenergetics. These results correlated with increased TFAM and vimentin-actin (VA) expression, representing a synthetic, overactive fibroblast phenotype. Finally, clinical samples from patients with OSMF exhibited a progressive increase in TFAM and VA-positive fibroblasts in advanced clinical disease, corroborating the in vitro observations. TGF-β1 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation.