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The Smad2/3/4 complex binds miR‐139 promoter to modulate TGFβ‐induced proliferation and activation of human Tenon's capsule fibroblasts through the Wnt pathway

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The activation and proliferation of human Tenon's fibroblasts (HTFs) play a vital role in the fibrosis in the pathology of the scar formation after the glaucoma filtration surgery. Transforming growth… Click to show full abstract

The activation and proliferation of human Tenon's fibroblasts (HTFs) play a vital role in the fibrosis in the pathology of the scar formation after the glaucoma filtration surgery. Transforming growth factor β1 (TGFβ1)/Smads signaling has been reported to promote fibrosis. In our previous study, we revealed that TGFβ1‐induced orbital fibroblast activation and proliferation through Wnt/β‐catenin signaling. As microRNA (miR)‐139 could target several factors in Wnt signaling to modulate fibrosis, here, the effect and mechanism of miR‐139 in HTF activation and proliferation were investigated. miR‐139 overexpression significantly reversed the TGFβ1‐induced increase in collagen I and α‐smooth muscle actin contents and proliferation in HTFs. CTNNB1 and CTNND1 were direct downstream of miR‐139 and can significantly restore the suppressive effect of miR‐139 on the activation and proliferation in HTFs under TGFβ1 stimulation. Smad2/3/4 complex inhibits the transcription activity of miR‐139, most possibly by Smad4 binding to the miR‐139 promoter. Taken together, we demonstrated a new mechanism of HTF activation and proliferation from the perspective of miRNA regulation, which may provide new strategies for improving the fibrosis after the glaucoma filtration surgery.

Keywords: mir 139; activation proliferation; tgf induced; proliferation

Journal Title: Journal of Cellular Physiology
Year Published: 2019

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