PMID- 30648255 OWN - NLM STAT- MEDLINE DCOM- 20200526 LR - 20221207 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 234 IP - 8 DP - 2019 Aug TI - The Smad2/3/4 complex binds miR-139 promoter to modulate TGFbeta-induced proliferation and activation of human Tenon's capsule fibroblasts through the Wnt pathway. PG - 13342-13352 LID - 10.1002/jcp.28011 [doi] AB - 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 beta1 (TGFbeta1)/Smads signaling has been reported to promote fibrosis. In our previous study, we revealed that TGFbeta1-induced orbital fibroblast activation and proliferation through Wnt/beta-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 TGFbeta1-induced increase in collagen I and alpha-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 TGFbeta1 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. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Deng, Mi AU - Deng M AD - Department of Ophthalmology, Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Hou, Shi-Ying AU - Hou SY AD - Department of Ophthalmology, Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Tong, Bo-Ding AU - Tong BD AD - Department of Ophthalmology, Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Yin, Jia-Yang AU - Yin JY AD - Department of Ophthalmology, Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Xiong, Wei AU - Xiong W AUID- ORCID: 0000-0002-3017-9895 AD - Department of Ophthalmology, Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190115 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (CTNNB1 protein, human) RN - 0 (Catenins) RN - 0 (MIRN139 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (SMAD2 protein, human) RN - 0 (SMAD3 protein, human) RN - 0 (SMAD4 protein, human) RN - 0 (Smad Proteins) RN - 0 (Smad2 Protein) RN - 0 (Smad3 Protein) RN - 0 (Smad4 Protein) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - 0 (beta Catenin) RN - 0 (Delta Catenin) SB - IM MH - Binding Sites/genetics MH - Catenins/antagonists & inhibitors/genetics/metabolism MH - Cell Proliferation MH - Cicatrix/etiology/metabolism/pathology MH - Fibroblasts/cytology/metabolism MH - Fibrosis MH - Glaucoma Drainage Implants/adverse effects MH - Humans MH - MicroRNAs/*genetics/metabolism MH - Promoter Regions, Genetic MH - Smad Proteins/*metabolism MH - Smad2 Protein/metabolism MH - Smad3 Protein/metabolism MH - Smad4 Protein/metabolism MH - Tenon Capsule/*cytology/*metabolism MH - Transforming Growth Factor beta1/metabolism MH - Wnt Signaling Pathway MH - beta Catenin/antagonists & inhibitors/genetics/metabolism MH - Delta Catenin OTO - NOTNLM OT - Smad2/3/4 complex OT - TGFbeta1 OT - human Tenon's fibroblasts (HTFs) OT - miR-139 OT - proliferation EDAT- 2019/01/17 06:00 MHDA- 2020/05/27 06:00 CRDT- 2019/01/17 06:00 PHST- 2018/11/02 00:00 [received] PHST- 2018/12/11 00:00 [accepted] PHST- 2019/01/17 06:00 [pubmed] PHST- 2020/05/27 06:00 [medline] PHST- 2019/01/17 06:00 [entrez] AID - 10.1002/jcp.28011 [doi] PST - ppublish SO - J Cell Physiol. 2019 Aug;234(8):13342-13352. doi: 10.1002/jcp.28011. Epub 2019 Jan 15.