Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/67808
Title: | Integrative miRNA and Gene Expression Profiling Analysis of Human Quiescent Hepatic Stellate Cells. |
Author: | Coll, Mar Taghdouini, Adil El Perea, Luis Mannaerts, Inge Vila Casadesús, Maria Blaya, Delia Rodrigo Torres, Daniel Affò, Silvia Morales-Ibanez, Oriol Graupera, Isabel Lozano Salvatella, Juan José Najimi, Mustapha Sokal, Etienne Lambrecht, Joeri Ginès i Gibert, Pere van Grunsven, Leo A. Sancho Bru, Pau |
Keywords: | Micro RNAs Malalties del fetge Expressió gènica MicroRNAs Liver diseases Gene expression |
Issue Date: | 22-Jun-2015 |
Publisher: | Nature Publishing Group |
Abstract: | Unveiling the regulatory pathways maintaining hepatic stellate cells (HSC) in a quiescent (q) phenotype is essential to develop new therapeutic strategies to treat fibrogenic diseases. To uncover the miRNA-mRNA regulatory interactions in qHSCs, HSCs were FACS-sorted from healthy livers and activated HSCs (aHSCs) were generated in vitro. MiRNA Taqman array analysis showed HSCs expressed a low number of miRNAs (n = 259), from which 47 were down-regulated and 212 up-regulated upon activation. Computational integration of miRNA and gene expression profiles revealed that 66% of qHSC-associated miRNAs correlated with more than 6 altered target mRNAs (17,28 ± 10,7 targets/miRNA) whereas aHSC-associated miRNAs had an average of 1,49 targeted genes. Interestingly, interaction networks generated by miRNA-targeted genes in qHSCs were associated with key HSC activation processes. Next, selected miRNAs were validated in healthy and cirrhotic human livers and miR-192 was chosen for functional analysis. Down-regulation of miR-192 in HSCs was found to be an early event during fibrosis progression in mouse models of liver injury. Moreover, mimic assays for miR-192 in HSCs revealed its role in HSC activation, proliferation and migration. Together, these results uncover the importance of miRNAs in the maintenance of the qHSC phenotype and form the basis for understanding the regulatory networks in HSCs. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1038/srep11549 |
It is part of: | Scientific Reports, 2015, vol. 5, p. 1-14 |
URI: | http://hdl.handle.net/2445/67808 |
Related resource: | http://dx.doi.org/10.1038/srep11549 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
653266.pdf | 2.01 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License