Stool Proteome analysis of biliary atresia after Kasai portoenterostomy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Jun Fujishiro
PROVIDER: PXD031394 | JPOST Repository | Thu Feb 02 00:00:00 GMT 2023
REPOSITORIES: jPOST
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Project description:Stool samples from three patients with Biliary atresia (BA), two patients with neonatal cholestasis of other etiologies (non-BA), and four healthy infants (H) were analyzed by overlapping DIA-MS.
2020-08-22 | PXD021051 | JPOST Repository
Project description:Stool samples from four patients with Biliary atresia (BA) and three patients with neonatal cholestasis of other etiologies (non-BA) were analyzed by overlapping DIA-MS.
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Project description:Biliary atresia (BA) is a progressive fibro-inflammatory disorder that is the leading indication for liver transplantation in children. Although there is evidence implicating genetic, infectious, environmental, and inflammatory causes, the etiology of BA remains unknown. We have recently reported that cholangiocytes from BA patients showed decreased DNA methylation relative to disease- and non-disease controls, supporting a potential role for DNA hypomethylation in BA etiopathogenesis.
2015-06-18 | GSE69948 | GEO
Project description:Biliary atresia (BA) is a progressive fibro-inflammatory disorder that is the leading indication for liver transplantation in children. Although there is evidence implicating genetic, infectious, environmental, and inflammatory causes, the etiology of BA remains unknown. We have recently reported that cholangiocytes from BA patients showed decreased DNA methylation relative to disease- and non-disease controls, supporting a potential role for DNA hypomethylation in BA etiopathogenesis. In the current study, we examined the methylation status of specific genes in human BA livers using methylation microarray technology. We found global DNA hypomethylation in BA samples as compared to disease- and non-disease controls at specific genetic loci. Hedgehog pathway members, SHH and GLI2, known to be upregulated in BA, were both hypomethylated, validating this approach as an investigative tool. Another region near the PDGFA locus was the most significantly hypomethylated in BA, suggesting potential aberrant expression. Validation assays confirmed increased transcriptional and protein expression of PDGFA in BA livers. We also show that PDGF-A protein is specifically localized to cholangiocytes in human liver samples. Injection of PDGF-AA protein dimer into zebrafish larvae caused biliary developmental and functional defects. In addition, activation of the Hedgehog pathway caused increased expression of PDGF-A in zebrafish larvae, providing a previously unrecognized link between PDGF and the Hedgehog pathway. DNA hypomethylation appears to be a specific factor in mediating overexpression of genes associated with BA. Our findings validate the role of Hedgehog pathway signaling and implicate PDGF as a new candidate for a role in BA pathogenesis.
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Project description:Background: RNASeq was performed on organoids derived from livers of normal healthy donors and patients with biliary atresia to characterize transcriptomic signatures. Methods: Organoids generated from livers of normal healthy donors and patients with biliary atresia were cultured either in expansion (undifferentiated: 3 NCOs and 11 BACOs) or differentiation medium (differentiated: 3 BACOs). Liver tissues obtained from deceased-donor subjects served as normal controls (N=3). Total RNA was isolated from organoids and liver biopsy tissue specimens. Results: Organoids from patients with biliary atresia showed abnormal cell polarity, loss of tight junctions, increased permeability and decreased expression of genes related to epidermal growth factor (EGF)- and fibroblast growth factor 2 (FGF2)-signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation and functional markers with restored cell polarity. Conclusion: Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell‐cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.
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Project description:Biliary atresia (BA) causes neonatal cholestasis jaundice. The primary therapeutic treatment for BA is the Kasai portoenterostomy, a surgical procedure creating a new bile duct to restore bile flow. However, current diagnostic approaches for BA are imprecise and time-consuming, making early diagnosis crucial for successful treatment outcomes. The present study was aimed to analyze proteins from peripheral blood mononuclear cells (PBMCs) obtained from children with biliary atresia compared with healthy children as potential biomarkers for diagnostic tests.
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