Open AccessMicroRNA Profiling Identifies miR‐29 as a Regulator of Disease‐associated Pathways in Experimental Biliary Atresia
Author(s) -
Hand Nicholas J.,
Horner Amber M.,
Master Zankhana R.,
Boateng LaTasha A.,
LeGuen Claire,
Uvaydova Marina,
Friedman Joshua R.
Publication year - 2012
Publication title -
journal of pediatric gastroenterology and nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 131
eISSN - 1536-4801
pISSN - 0277-2116
DOI - 10.1097/mpg.0b013e318244148b
Subject(s) - biliary atresia , microrna , medicine , cholestasis , messenger rna , pathogenesis , downregulation and upregulation , gene expression , biology , gene , pathology , genetics , liver transplantation , transplantation
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.