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Background/aims

Wnt/β-catenin pathway is involved in liver fibrosis and microRNAs (miRNAs) are considered as key regulators of the activation of hepatic stellate cells (HSCs). A recent study showed the protective role of miR-378a-3p against cardiac fibrosis. However, whether miR-378a-3p suppresses Wnt/β-catenin pathway in liver fibrosis is largely unknown.

Methods

miR-378a-3p expression was detected in carbon tetrachloride-induced liver fibrosis and activated HSCs. Effects of miR-378a-3p overexpression on HSC activation and Wnt/β-catenin pathway were analyzed. Bioinformatic analysis was employed to identify the potential targets of miR-378a-3p. Serum miR-378a-3p expression was analyzed in patients with cirrhosis.

Results

Reduced miR-378a-3p expression was observed in the fibrotic liver tissues and activated HSCs. Up-regulation of miR-378a-3p inhibited HSC activation including cell proliferation, α-smooth muscle actin (α-SMA) and collagen expression. Moreover, miR-378a-3p overexpression resulted in Wnt/β-catenin pathway inactivation. Luciferase reporter assays demonstrated that Wnt10a, a member of Wnt/β-catenin pathway, was confirmed to be a target of miR-378a-3p. By contrast, miR-378a-3p inhibitor contributed to HSC activation, with an increase in cell proliferation, α-SMA and collagen expression. But all these effects were blocked down by silencing of Wnt10a. Notably, sera from patients with cirrhosis contained lower levels of miR-378a-3p than sera from healthy controls. Receiver operating characteristic curve analysis suggested that serum miR-378a-3p differentiated liver cirrhosis patients from healthy controls, with an area under the curve of ROC curve of 0.916.

Conclusion

miR-378a-3p suppresses HSC activation, at least in part, via targeting of Wnt10a, supporting its potential utility as a novel therapeutic target for liver fibrosis."xsd:string
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http://purl.uniprot.org/citations/27832641http://purl.uniprot.org/core/author"Chen B."xsd:string
http://purl.uniprot.org/citations/27832641http://purl.uniprot.org/core/author"Fan X."xsd:string
http://purl.uniprot.org/citations/27832641http://purl.uniprot.org/core/author"Zheng J."xsd:string
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http://purl.uniprot.org/citations/27832641http://purl.uniprot.org/core/author"Dong P."xsd:string
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http://purl.uniprot.org/citations/27832641http://purl.uniprot.org/core/name"Cell Physiol Biochem"xsd:string
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http://purl.uniprot.org/citations/27832641http://purl.uniprot.org/core/title"Activation of Hepatic Stellate Cells is Inhibited by microRNA-378a-3p via Wnt10a."xsd:string
http://purl.uniprot.org/citations/27832641http://purl.uniprot.org/core/volume"39"xsd:string
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