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Arch Biochem Biophys. 2015 Jan 15;566:49-57. doi: 10.1016/j.abb.2014.12.007. Epub 2014 Dec 15.

Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition.

Author information

1
Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
2
Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA; Department of Physiology, Luzhou Medical College, Luzhou, Sichuan, People's Republic of China.
3
Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA. Electronic address: lin.liu@okstate.edu.

Abstract

Idiopathic pulmonary fibrosis (IPF) is one of the most common and severe interstitial lung diseases. Epithelial-to-mesenchymal transition (EMT) is a process whereby epithelial cells undergo transition to a mesenchymal phenotype. This process has been shown to contribute to IPF. MicroRNAs (miRNAs) are small non-coding RNAs of 18-24 nucleotides in length which regulate gene expression. Several studies have implicated miRNAs in EMT; however, specific miRNAs that regulate EMT in IPF have not yet been identified. In this study, we identified 6 up-regulated and 3 down-regulated miRNAs in a human lung epithelial cell EMT model using miRNA microarray and real-time PCR. Overexpression of one of these up-regulated miRNAs, miR-424, increased the expression of α-smooth muscle actin, an indicator of myofibroblast differentiation, but had no effects on the epithelial or mesenchymal cell markers. miR-424 enhanced the activity of the TGF-β signaling pathway, as demonstrated by a luciferase reporter assay. Further experiments showed that miR-424 decreased the protein expression of Smurf2, a negative regulator of TGF-β signaling, indicating that miR-424 exerts a forward regulatory loop in the TGF-β signaling pathway. Our results suggest that miR-424 regulates the myofibroblast differentiation during EMT by potentiating the TGF-β signaling pathway, likely through Smurf2.

KEYWORDS:

Epithelial-to-mesenchymal transition; Idiopathic pulmonary fibrosis; Myofibroblast differentiation; Smurf2; TGF-β; miR-424

PMID:
25524739
PMCID:
PMC4297572
DOI:
10.1016/j.abb.2014.12.007
[Indexed for MEDLINE]
Free PMC Article

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