Affiliations: [a] Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China | [b] Department of Critical Care Medicine, the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China
Correspondence:
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Corresponding author: Qulian Guo, Department of Anesthesiology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha 410008, Hunan, China. Tel.: +86 731 84327411; Fax: +86 731 84327411;qulianguo@hotmail.com
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.
METHODS AND 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.
