کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1925042 1536336 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition
چکیده انگلیسی


• Identified 6 up-regulated and 3 down-regulated miRNAs in lung epithelial cell EMT.
• miR-424 increased the expression of α-smooth muscle actin.
• miR-424 enhanced the activity of the TGF-β signaling pathway.
• miR-424 decreased the protein expression of Smurf2.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 566, 15 January 2015, Pages 49–57
نویسندگان
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