PUBLICATION
BETA-AMYLOID DEPOSIT IN BILIARY ATRESIA REDUCES LIVER REGENERATION VIA INHIBITING ENERGY METABOLISM AND mTOR SIGNALING
- Authors
- Tian, X., Wang, Y., Zhou, Y., Wu, B., Lu, Y., Du, J., Wang, W., Cai, W., Xiao, Y.
- ID
- ZDB-PUB-220923-17
- Date
- 2022
- Source
- Clinical and translational gastroenterology 13(11): e00536 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Humans
- Animals
- Mice
- Energy Metabolism
- TOR Serine-Threonine Kinases
- Liver Regeneration*
- Biliary Atresia*
- Zebrafish
- PubMed
- 36137184 Full text @ Clin Transl Gastroenterol
Citation
Tian, X., Wang, Y., Zhou, Y., Wu, B., Lu, Y., Du, J., Wang, W., Cai, W., Xiao, Y. (2022) BETA-AMYLOID DEPOSIT IN BILIARY ATRESIA REDUCES LIVER REGENERATION VIA INHIBITING ENERGY METABOLISM AND mTOR SIGNALING. Clinical and translational gastroenterology. 13(11):e00536.
Abstract
Background Biliary atresia (BA) is a devastating obstructive bile duct disease of newborns. This study aims to investigate the roles and involved mechanisms of beta-amyloid (Aβ) in the pathogenesis of BA.
Methods We examined the distribution of Aβ protein and its precursor in the livers of BA patients. A murine liver organoid and a zebrafish model were established to investigate the exact roles of Aβ in liver regeneration for BA.
Results Both Aβ mRNA and protein significantly increased in livers of BA infants and deposited around the central vein. In the plasma, Aβ elevated significantly in BA patients and positively correlated with liver injury progression. In vitro, Aβ treatment induced abnormal morphology and caused impaired growth in liver organoids. Energy metabolism analysis demonstrated Aβ increased aerobic glycolysis and reduced ATP synthase in organoids, in which the mammalian target of rapamycin (mTOR) signaling was suppressed. In vivo, Aβ42 exposure caused liver degeneration in zebrafish larvae.
Conclusion Aβ depositing in livers of BA infants reduced the liver regeneration via attenuating mitochondrial respiration and mTOR signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping