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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, 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
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.
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It is part of: Scientific Reports, 2015, vol. 5, p. 1-14
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Medicina)

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