Abstract
Scar formation resulting from overly active wound healing is a critical factor in the success rate of glaucoma filtration surgery (GFS). IL-6 and TGF-β have been implicated in the pathogenesis of fibrogenesis. In addition, the signal transducer and activator of transcription 3 (STAT3) can be activated by numerous cytokines and growth factors, including IL-6 and TGF-β1. Thus, STAT3 activation may integrate common profibrotic pathways to promote fibrosis. In this study, an increase in p-STAT3 was observed in activated HTFs. Inhibiting STAT3 in cultured HTFs by pharmacological inactivation reversed the fibrotic responses, such as fibroblast migration, the differentiation of resting fibroblasts into myofibroblasts and the deposition of ECM, mediated by IL-6 and TGF-β1. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3) was decreased in HTFs cultured with IL-6 and TGF-β1, and SOCS3 overexpression rescued ECM deposition, α-SMA expression and migration in IL-6- and TGF-β1-stimulated HTFs by inactivating STAT3. Finally, S3I-201 treatment inhibited profibrotic gene expression and subconjunctival fibrosis in a rat model of GFS. In conclusion, our data suggests that STAT3 plays a central role in fibrosis induced by different profibrotic pathways and that STAT3 is a potential target for antifibrotic therapies following GFS.