MEK inhibition prevents TGF-β1-induced myofibroblast transdifferentiation in human tenon fibroblasts

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Abstract

Subconjunctival fibrosis represents the primary cause of postoperative failure of trabeculectomy, and at present there is a lack of effective intervention strategies. The present study aimed to investigate the effect of the mitogen-activated protein kinase kinase (MEK) inhibitor U0126 on human tenon fibroblast (HTF) myofibrosis transdifferentiation, and to illuminate the underlying molecular mechanisms involved. It was demonstrated that U0126 significantly inhibited the proliferation, migration and collagen contraction of HTFs stimulated with TGF-β1. In addition, U0126 largely attenuated the TGF-β1-induced conversion of HTFs into myofibroblasts, as indicated by a downregulation of the mRNA and protein expression of α-smooth muscle actin and zinc finger protein SNAI1, and by ameliorating the 3D-collagen contraction response. Mechanistically, U0126 suppressed the TGF-β1-stimulated phosphorylation of mothers against decapentaplegic homolog 2/3, P38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2, indicating that U0126 may inhibit HTF activation through the canonical and non-canonical signaling pathways of TGF-β1. Therefore, U0126 exhibits a potent anti-fibrotic effect among HTFs, and the inhibition of MEK signaling may serve as an alternative intervention strategy for the treatment of trabeculectomy-associated fibrosis.

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APA

Wen, J., Lin, X., Gao, W., Qu, B., Ling, Y., Liu, R., & Yu, M. (2019). MEK inhibition prevents TGF-β1-induced myofibroblast transdifferentiation in human tenon fibroblasts. Molecular Medicine Reports, 19(1), 468–476. https://doi.org/10.3892/mmr.2018.9673

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