MicroRNA200a suppresses epithelialtomesenchymal transition in rat hepatic stellate cells via GLI family zinc finger 2.
Mol Med Rep
; 12(6): 8121-8, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26499180
ABSTRACT
Hepatic stellate cells (HSCs) have an important role in liver fibrosis. Epithelialtomesenchymal transition (EMT), which is promoted by the Hedgehog (Hh) signaling pathway, is involved in the activation of HSCs. MicroRNAs (miRNAs/miRs) have been reported to be involved in the progression of liver fibrosis. A previous study indicated that the activation of HSCs was suppressed by miR200a via targeting transforming growth factorß2 and ßcatenin. However, whether miR200a is able to regulate the EMT in HSCs has remained elusive. The present study revealed that miR200a was decreased in vitro and in vivo during liver fibrosis. Furthermore, miR200a overexpression resulted in the inhibition of proliferation, αSMA expression and extracellular matrix production of activated HSCs. Of note, miR200a overexpression reduced myofibroblastic markers, including αSMA, type I collagen and desmin, and increased the epithelial cell marker Ecadherin. These results were further confirmed by immunofluorescence staining. Further study showed that the expression of genes associated with Hh signaling, including Hhip, Shh and Gli1, were not affected by miR200a. However, Gli2, a downstream signaling protein of the Hh pathway, was inhibited by miR200a and confirmed as a target of miR200a using a dual luciferase reporter assay. In addition, the inhibition of the Hh pathway by miR200a resulted in an increase of BMP7 and Id2 as well as a reduction of Snai1 and S100A4. Collectively, the results of the present study demonstrated that miR200a suppressed the EMT process in HSCs, at least in part, via Gli2.
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Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Fatores de Transcrição Kruppel-Like
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article