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Update on investigations pertaining to the pathogenesis of biliary atresia.

ABSTRACT: Biliary atresia is a devastating biliary disease of neonates that results in liver transplantation for the vast majority. The etiology of biliary atresia is unknown and is likely multifactorial, with components of genetic predisposition, environmental trigger and autoimmunity contributing to disease pathogenesis. This review highlights recent work related to investigations of disease pathogenesis in biliary atresia.

SUBMITTER: Kilgore A

PROVIDER: S-EPMC5894874 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Update on investigations pertaining to the pathogenesis of biliary atresia.

Kilgore Alexandra A Mack Cara L CL

Pediatric surgery international 20171024 12

Biliary atresia is a devastating biliary disease of neonates that results in liver transplantation for the vast majority. The etiology of biliary atresia is unknown and is likely multifactorial, with components of genetic predisposition, environmental trigger and autoimmunity contributing to disease pathogenesis. This review highlights recent work related to investigations of disease pathogenesis in biliary atresia. ...[more]

PMID: 29063959

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Integrative genomics identifies candidate microRNAs for pathogenesis of experimental biliary atresia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-10-15 | E-GEOD-41595 | biostudies-arrayexpress

Integrative genomics identifies candidate microRNAs for pathogenesis of experimental biliary atresia

Project description:This SuperSeries is composed of the SubSeries listed below.

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Prominin-1 Promotes Biliary Fibrosis Associated With Biliary Atresia.

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MicroRNA-29b/142-5p contribute to the pathogenesis of biliary atresia by regulating the IFN-? gene.

Project description:Biliary atresia is one of the most common liver disease in infancy. The cause and pathogenesis remain largely unknown. This study aimed to investigate the potential regulatory effect of miR-29b/142-5p on IFN-? gene methylation. miRNAs microarray was performed on four pairs of liver and blood specimens from biliary atresia and choledochal cysts. We found the overexpression of miR-142-5p and mRNA level of DNA methyltransferase (DNMT) 1, and miR-29b and DNMT3a/DNMT3b were significantly negatively correlated in biliary atresia livers. Meanwhile, the methylation of the LINE-1, ALU and SAT2 repetitive sequences and the IFN-? promoter was lower, but the expression of IFN-? was upregulated. After transfected with DNMTs siRNAs, downregulation of DNMTs exerted a significant hypomethylating effect on the repetitive sequences, which led to upregulation of IFN-? in Jurkat cells. The direct interactions between miR-29b and DNMT3a/3b, and miR-142-5p and DNMT1 were identified using luciferase reporter assays. By transfecting mimics of miR-29b/142-5p into Jurkat cells, we found overexpression of miR-29b/142-5p markedly suppressed expression of DNMTs. Furthermore, the methylation of repetitive sequences and the IFN-? promoter region were remarkably downregulated, and with elevated IFN-? expression. After transfecting the miRNA inhibitors, the levels of DNMTs and the methylation of the IFN-? gene promoter region was upregulated, while levels of IFN-? were markedly suppressed. Our study suggested that miRNA-29b/142-5p overexpression and targeted inhibition of DNMTs expression resulted in decreased overall gene methylation and overexpression of the methylation-sensitive IFN-? gene.

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