Beta-amyloid deposition around hepatic bile ducts is a novel pathobiological and diagnostic feature of biliary atresia
| Autor: | Ben Niu, Paul K.H. Tam, Zhongluan Wu, Yan Chen, Bin Wang, Rachel Sze Wan Yiu, Kenneth K. Y. Wong, Ruizhong Zhang, Patrick Ho Yu Chung, Michelle Yu, Huimin Xia, Vincent C.H. Lui, Rosana Ottakandathil Babu, Yongqin Ye, Michael Qi Zhang, Urban Lendahl |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty medicine.medical_treatment Liver transplantation Cholangiocyte Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Biliary atresia Biliary Atresia medicine Organoid Animals Humans Amyloid beta-Peptides Hepatology business.industry Bile duct Gene Expression Profiling medicine.disease Peptide Fragments Organoids Disease Models Animal 030104 developmental biology medicine.anatomical_structure Hepatocyte Hepatocytes 030211 gastroenterology & hepatology Cerebral amyloid angiopathy Bile Ducts business Transcriptome |
| Zdroj: | Journal of hepatology. 73(6) |
| ISSN: | 1600-0641 |
| Popis: | Background and Aims Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aimed to investigate the underlying pathogenesis and molecular signatures associated with BA. Methods We combined organoid and transcriptomic analysis to gain new insights into BA pathobiology using patient samples and a mouse model of BA. Results Liver organoids derived from patients with BA and a rhesus rotavirus A-infected mouse model of BA, exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures and altered beta-amyloid-related gene expression. Beta-amyloid accumulation was observed around the bile ducts in BA livers and exposure to beta-amyloid induced the aberrant morphology in control organoids. Conclusion The novel observation that beta-amyloid accumulates around bile ducts in the livers of patients with BA has important pathobiological implications, as well as diagnostic potential. Lay summary Biliary atresia is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. Using human and mouse ‘liver mini-organs in the dish’, we unexpectedly identified beta-amyloid deposition – the main pathological feature of Alzheimer's disease and cerebral amyloid angiopathy – around bile ducts in livers from patients with biliary atresia. This finding reveals a novel pathogenic mechanism that could have important diagnostic and therapeutic implications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect