Coordinate expression of regulatory genes differentiates embryonic and perinatal forms of biliary atresia

Abstract

The molecular basis for the embryonic and perinatal clinical forms of biliary atresia is largely undefined. In this study, we aimed to: 1) determine if the clinical forms can be differentiated at the transcriptional level, and 2) search for molecular mechanisms underlying phenotypic differences. To this end, we generated biotinylated cRNA probes from livers of age-matched infants with the embryonic (n ‫؍‬ 5) and perinatal (n ‫؍‬ 6) forms of biliary atresia at the time of diagnosis and hybridized them against the Affymetrix human HG-U133 A and B microarrays containing 44,760 gene products. Data filtering and two-way cluster analysis of the gene expression platform identified 230 genes with an expression profile that is highly distinctive of the clinical phenotypes. Functionally, the profile did not reveal a higher-order function for a specific cell type; instead, it uncovered a coordinated expression of regulatory genes. These regulatory genes were predominantly represented in the embryonic form (45% of genes), with a unique pattern of expression of genes involved in chromatin integrity/function (Smarca-1, Rybp, and Hdac3) and the uniform overexpression of five imprinted genes (Igf2, Peg3, Peg10, Meg3, and IPW), implying a failure to downregulate embryonic gene programs. In conclusion, embryonic and perinatal forms of biliary atresia are distinguished by gene expression profiling. The coordinate expression of regulators of chromatin structure/ function and of imprinted genes provides evidence for a transcriptional basis for the pathogenesis of the embryonic form of biliary atresia. Further studies exploring these biological processes are required to determine the significance of these findings. Supplementary material for this article can be found at http://genet.cchmc.org. (HEPATOLOGY 2004;39:954 -962.)

Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells

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Extrahepatic biliary atresia: current concepts and future directions

“…A obstrução se estende ao porta hepatis, e não existem lumens proximais para anastomose no porta hepatis. 57 , o que evidencia a influência de fatores epigenéticos na obliteração das vias biliares.…”

Case Report of Infantile Cholestasis with Liver Hemangioma

“…Liver enzymes ALT, AST, alkaline phosphatase, and GGT are included in the evaluation, although none is capable of diagnosing a particular condition. Protime/INR and albumin are tests of hepatic protein synthetic function [1][2][3][4][5][6][7][8][9][10].…”

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