title: miR-29 mediates TGFβ1-induced extracellular matrix synthesis through activation of PI3K-AKT pathway in human lung fibroblasts.
abstract: TGFβ1 is very important in the synthesis and degradation of extracellular matrix, and also in the mediation of human lung fibroblasts proliferation, and miR-29 plays an important role in this process. To explore the interactions of miR-29 family members and TGFβ1, the effects of transforming growth factor TGFβ1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFβ1 were examined in human lung fibroblasts. Treatment of the human embryonic lung fibroblast cell line IMR90 with TGFβ1 caused a decrease in expression of miR-29a/b/c by real-time PCR analysis. TGFβ1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFβ1-induced phenotype changes in IMR90 cells. Western blot analyses showed that TGFβ1 treatment unchanged total protein expression levels of PI3K or AKT, but the expression levels of p-PI3K, p-AKT, and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked phosphorylation of PI3K or AKT and decreased expression of COL1A1 after TGFβ1 treatment. The results indicate that TGFβ1 beta uses the PI3k-Akt pathway in these embryonic fibroblasts and miR29 blocks this activation pathway. It indicates a novel biological function of the PI3K-Akt pathway in IMR90. Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human lung fibroblasts.
authors.affiliation: National Engineering Laboratory for Rice and By-product Deep Processing, Central South University of Forestry and Technology, Changsha 410004, Hunan Province, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Qinlu
authors.initials: Q
authors.lastname: Lin
authors.forename: Junwen
authors.initials: J
authors.lastname: Liu
authors.forename: Feijun
authors.initials: F
authors.lastname: Luo
authors.forename: Xinhua
authors.initials: X
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhuang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053773:Transforming Growth Factor beta1; C532045:MIRN29a microRNA, human; C508960:TGFB1 protein, human