title: MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experimental biliary atresia.
abstract: Biliary atresia (BA) is a pediatric liver disease of unknown underlying etiology, in which fibroinflammatory destruction of the extrahepatic biliary system leads to obstructive cholestasis. MicroRNAs are a class of short (18-23 nucleotide), noncoding RNA molecules, which act as negative regulators of target mRNA stability and translation. The importance of these molecules in normal and diseased liver has been demonstrated, but their potential role in the pathogenesis of BA has not been addressed. We have profiled changes in liver microRNA levels in an established mouse model of the disease, identified significantly altered transcripts, and defined the spatial expression patterns of selected microRNAs. Two of these, miR-29a/29b1, are upregulated in experimental BA. Using antisense oligonucleotide-mediated inhibition in mice, we have delineated the full set of hepatic genes regulated by miR-29 and identified 2 mRNA targets of potential pathological relevance in experimental BA, Igf1 and Il1RAP. We have used reporter assays to confirm that Igf1 and Il1RAP are direct targets of miR-29.
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia Research Institute, ARC 902G, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hand
authors.forename: Amber M
authors.initials: AM
authors.lastname: Horner
authors.forename: Zankhana R
authors.initials: ZR
authors.lastname: Master
authors.forename: LaTasha A
authors.initials: LA
authors.lastname: Boateng
authors.forename: Claire
authors.initials: C
authors.lastname: LeGuen
authors.forename: Marina
authors.initials: M
authors.lastname: Uvaydova
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Friedman
mesh_terms: D000818:Animals; D001656:Biliary Atresia / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020320:Oligoribonucleotides, Antisense / Q000037:antagonists & inhibitors; D059467:Transcriptome
chemical_list: D005819:Genetic Markers; C507767:Il1rap protein, mouse; D053577:Interleukin-1 Receptor Accessory Protein; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D020320:Oligoribonucleotides, Antisense; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I