title: MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts.
abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3'-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF-collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China. Electronic address: wenfuqiang.scu@gmail.com.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wen
mesh_terms: D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology*; D035683:MicroRNAs / Q000235:genetics*; D013329:Structure-Activity Relationship; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; C528163:MIRN26 microRNA, human
keywords: Cell cycle; Lung fibroblasts; MicroRNAs; Proliferation; Transforming growth factor beta one; Transforming growth factor beta receptors I