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http://purl.uniprot.org/citations/27165825http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27165825http://www.w3.org/2000/01/rdf-schema#comment"Chronic kidney disease is associated with progressive renal fibrosis, where perivascular cells give rise to the majority of α-smooth muscle actin (α-SMA) positive myofibroblasts. Here we sought to identify pericytic miRNAs that could serve as a target to decrease myofibroblast formation. Kidney fibrosis was induced in FoxD1-GC;Z/Red-mice by unilateral ureteral obstruction followed by FACS sorting of dsRed-positive FoxD1-derivative cells and miRNA profiling. MiR-132 selectively increased 21-fold during pericyte-to-myofibroblast formation, whereas miR-132 was only 2.5-fold up in total kidney lysates (both in obstructive and ischemia-reperfusion injury). MiR-132 silencing during obstruction decreased collagen deposition (35%) and tubular apoptosis. Immunohistochemistry, Western blot, and qRT-PCR confirmed a similar decrease in interstitial α-SMA(+) cells. Pathway analysis identified a rate-limiting role for miR-132 in myofibroblast proliferation that was confirmed in vitro. Indeed, antagomir-132-treated mice displayed a reduction in the number of proliferating Ki67(+) interstitial myofibroblasts. Interestingly, this was selective for the interstitial compartment and did not impair the reparative proliferation of tubular epithelial cells, as evidenced by an increase in Ki67(+) epithelial cells, as well as increased phospho-RB1, Cyclin-A and decreased RASA1, p21 levels in kidney lysates. Additional pathway and gene expression analyses suggest miR-132 coordinately regulates genes involved in TGF-β signaling (Smad2/Smad3), STAT3/ERK pathways, and cell proliferation (Foxo3/p300). Thus, silencing miR-132 counteracts the progression of renal fibrosis by selectively decreasing myofibroblast proliferation and could potentially serve as a novel antifibrotic therapy."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.org/dc/terms/identifier"doi:10.1016/j.kint.2016.01.029"xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"van Gils J.M."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"van Zonneveld A.J."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"van Solingen C."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"Duijs J.M."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"Rabelink T.J."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"de Bruin R.G."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"van der Veer E.P."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"Humphreys B.D."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/author"Bijkerk R."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/name"Kidney Int"xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/pages"1268-1280"xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/title"Silencing of microRNA-132 reduces renal fibrosis by selectively inhibiting myofibroblast proliferation."xsd:string
http://purl.uniprot.org/citations/27165825http://purl.uniprot.org/core/volume"89"xsd:string
http://purl.uniprot.org/citations/27165825http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27165825
http://purl.uniprot.org/citations/27165825http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27165825
http://purl.uniprot.org/uniprot/#_Q61345-mappedCitation-27165825http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27165825
http://purl.uniprot.org/uniprot/#_Q3UQ37-mappedCitation-27165825http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27165825
http://purl.uniprot.org/uniprot/Q61345http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27165825
http://purl.uniprot.org/uniprot/Q3UQ37http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27165825