Aims: TGF-β-induced alveolar epithelial cells apoptosis were involved in idiopathic pulmonary fibrosis (IPF). This study aimed to explore potential targets and mechanisms of IPF.
Main methods: mRNA and microRNA arrays were used to analyze differentially expressed genes and miRNAs. Several essential targets of TGF-β-SMADs and TGF-β-PI3K-AKT pathways were detected.
Key findings: miR-31 and miR-184 expression levels were positively correlated with smad6 and smad2/akt expression levels in IPF patients. TGF-β could induce miR-31 and suppress miR-184 levels in A549 cells. miR-31 was confirmed to bind to the smad6-3'UTR and functionally suppress its expression. Down-regulated SMAD6 enhanced SMAD2/SMAD4 dimer formation and translocation due to its failure to prevent SMAD2 phosphorylation. In contrast, anti-fibrotic functions of miR-184 were abolished due to TGF-β directly suppressing miR-184 levels in A549 cells. When A549 was stimulated by TGF-β combined with or without miR-31 inhibitor/miR-184 mimic, it was showed that depleted miR-31 and/or increased miR-184 significantly ameliorated TGF-β-induced viability of A549 cells, as well as inhibited the expression of profibrotic factors, MMP7 and RUNX2.
Significance: Inhibiting miR-31 and/or promoting miR-184 protect against TGF-β-induced fibrogenesis by respectively repressing the TGF-β-SMAD2 and TGF-β-PI3K-AKT signaling pathways, implying that miR-31/184 are potential targets and suggesting a new management strategy for IPF.
Keywords: Alveolar epithelial cells; Apoptosis; Idiopathic pulmonary fibrosis; Micro RNA; TGF-β signaling pathway.
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