title: MiR-29 mediates TGFβ 1-induced extracellular matrix synthesis through activation of Wnt/β -catenin pathway in human pulmonary fibroblasts.
abstract: BACKGROUND
  TGFβ 1 is very important in the synthesis and degradation of extracellular matrix (ECM), and also in the mediation of human pulmonary fibroblasts proliferation, and miR-29 plays an important role in this process.
  
  
  OBJECTIVE
  In the present study, the effects of TGFβ 1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFβ 1 were examined in human pulmonary fibroblasts.
  
  
  RESULTS
  Treatment of the human IMR-90 cells with TGFβ 1 caused a decrease in the expression of miR-29a/b/c as determined by real-time PCR analysis. TGFβ 1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFβ 1-induced phenotype changes in IMR-90. Western blot analyses showed that TGFβ 1 treatment unchanged total protein expression levels of β -catenin, but phosphorylation of β -catenin and the expression levels of wnt3a and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked DKK1, wnt3a, and phosphorylation of β -catenin and decreased expression of COL1A1 after TGFβ 1 treatment. Our results showed that TGFβ 1 activated the wnt/β -catenin pathway, and this activation was essential for the expression of miR-29 in IMR-90.
  
  
  CONCLUSIONS
  The results indicate a novel biological function of the wnt/β -catenin pathway in IMR-90. Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human IMR-90.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Department of Critical Care Medicine, the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.
authors.forename: Jingshi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Qulian
authors.initials: Q
authors.lastname: Guo
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000096:biosynthesis; D000090602:Collagen Type I, alpha 1 Chain; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008168:Lung; D035683:MicroRNAs / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D051176:beta Catenin
keywords: PI3K-AKT; TGFβ 1; miR-29; pulmonary fibrosis