MEK inhibition prevents TGF-β1-induced myofibroblast transdifferentiation in human tenon fibroblasts
| Autor: | Xianchai Lin, Yunlan Ling, Rongjiao Liu, Jiamin Wen, Bo Qu, Wuyou Gao, Minbin Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research p38 mitogen-activated protein kinases Down-Regulation Biochemistry Transforming Growth Factor beta1 03 medical and health sciences Downregulation and upregulation Cell Movement Nitriles Genetics Butadienes Humans subconjunctival fibrosis human tenon fibroblasts RNA Messenger Phosphorylation Protein kinase A Myofibroblasts Molecular Biology transforming growth factor-β1 Cells Cultured Cell Proliferation glaucoma filtration surgery Chemistry Kinase Transdifferentiation Cell Differentiation Articles Fibroblasts Fibrosis Actins Cell biology mitogen-activated protein kinase kinase inhibitor 030104 developmental biology Oncology Mitogen-Activated Protein Kinase Kinase Inhibitor Cell Transdifferentiation Molecular Medicine Collagen Snail Family Transcription Factors Signal transduction Mitogen-Activated Protein Kinases Myofibroblast Signal Transduction |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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