PUBLICATION
Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease
- Authors
- Tokumaru, T., Apolinario, M.E.C., Shimizu, N., Umeda, R., Honda, K., Shikano, K., Teranishi, H., Hikida, T., Hanada, T., Ohta, K., Li, Y., Murakami, K., Hanada, R.
- ID
- ZDB-PUB-240403-9
- Date
- 2024
- Source
- Scientific Reports 14: 78137813 (Journal)
- Registered Authors
- Hanada, Reiko, Hanada, Toshikatsu
- Keywords
- none
- MeSH Terms
-
- Adenosine
- Adenosine Triphosphate
- Animals
- Disease Progression
- Fatty Liver*
- Liver Cirrhosis
- Liver Neoplasms*
- Metabolic Diseases*
- Perciformes*
- Zebrafish
- PubMed
- 38565862 Full text @ Sci. Rep.
Citation
Tokumaru, T., Apolinario, M.E.C., Shimizu, N., Umeda, R., Honda, K., Shikano, K., Teranishi, H., Hikida, T., Hanada, T., Ohta, K., Li, Y., Murakami, K., Hanada, R. (2024) Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease. Scientific Reports. 14:78137813.
Abstract
Steatotic liver disease (SLD) is a burgeoning health problem predominantly associated with excessive alcohol consumption, which causes alcohol-related liver disease (ALD), and high caloric intake, which results in metabolic dysfunction-associated SLD (MASLD). The pathogenesis of ALD and MASLD, which can progress from steatohepatitis to more severe conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma, is complicated by several factors. Recently, extracellular ATP and adenosine (Ado), as damage-associated molecular patterns, were reported to promote inflammation and liver fibrosis, contributing to SLD pathogenesis. Here, we explored the in vivo dynamics of hepatic extracellular ATP and Ado during the progression of steatohepatitis using a genetically encoded GPCR-activation-based sensor (GRAB) in zebrafish models. We established hepatocyte-specific GRABATP and GRABAdo in zebrafish and investigated the changes in in vivo hepatic extracellular ATP and Ado levels under ALD or MASLD conditions. Disease-specific changes in hepatocyte extracellular ATP and Ado levels were observed, clearly indicating a correlation between hepatocyte extracellular ATP/Ado dynamics and disease progression. Furthermore, clodronate, a vesicular nucleotide transporter inhibitor, alleviated the MASLD phenotype by reducing the hepatic extracellular ATP and Ado content. These findings provide deep insights into extracellular ATP/Ado dynamics in disease progression, suggesting therapeutic potential for ALD and MASLD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping