ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2018
Transcription factor GATA6: a novel marker and putative inducer of ductal metaplasia in biliary atresia.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Biomarkers for the diagnosis and post-Kasai portoenterostomy prognosis of biliary atresia: a systematic review and meta-analysis.Scientific reports · 2021Pooled it
- Dental pulp stem cells maintain epigenetic chromatin architecture remodeling primed by the etiological stimulus of biliary atresia.Stem cell research & therapy · 2026Article
- Fibrotic liver injury in biliary atresia: long-term implications.World journal of pediatric surgery · 2025Review
- Biliary Atresia Animal Models: Is the Needle in a Haystack?International journal of molecular sciences · 2022Review
- Role of Immune Cells in Biliary Repair.Frontiers in immunology · 2022Review
- GATA6 modulates the ductular reaction to bile duct ligation.Hepatology international · 2021Article
- Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration.JCI insight · 2020Article
- Functional Profiling of FSH and Estradiol in Ovarian Granulosa Cell Tumors.Journal of the Endocrine Society · 2020Article
- Epigenomic signatures in liver and blood of Wilson disease patients include hypermethylation of liver-specific enhancers.Epigenetics & chromatin · 2019Article
- Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma.Journal of liver · 2018Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Biliary atresia (BA), a neonatal liver disease, is characterized by obstruction of extrahepatic bile ducts with subsequent cholestasis, inflammation, and progressive liver fibrosis. To gain insights into the pathophysiology of BA, we focused attention on GATA6, a transcription factor implicated in biliary development. Early in fetal development GATA6 expression is evident in cholangiocytes and hepatocytes, but by late gestation it is extinguished in hepatocytes. Utilizing a unique set of BA liver samples collected before and after successful portoenterostomy (PE), we found that GATA6 expression is markedly upregulated in hepatocytes of patients with BA compared with healthy and cholestatic disease controls. This upregulation is recapitulated in two murine models simulating bile duct obstruction and intrahepatic bile ductule expansion. GATA6 expression in BA livers correlates with two established negative prognostic indicators (age at PE, degree of intrahepatic bile ductule expansion) and decreases after normalization of serum bilirubin by PE. GATA6 expression in BA livers correlates with expression of known regulators of cholangiocyte differentiation ( JAGGED1, HNF1β, and HNF6). These same genes are upregulated after enforced expression of GATA6 in human hepatocyte cell models. In conclusion, GATA6 is a novel marker and a putative driver of hepatocyte-cholangiocyte metaplasia in BA, and its expression in hepatocytes is downregulated after successful PE. NEW & NOTEWORTHY A pathological hallmark in the liver of patients with biliary atresia is ductular reaction, an expansion of new bile ductules that are thought to arise from conversion of mature hepatocytes. Here, we show that transcription factor GATA6 is a marker and potential driver of hepatocyte ductal metaplasia in biliary atresia. Hepatocyte GATA6 expression is elevated in biliary atresia, correlates with bile duct expansion, and decreases after successful portoenterostomy.
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