PUBLICATION
Glia maturation factor-β in hepatocytes enhances liver regeneration and mitigates steatosis and ballooning in zebrafish
- Authors
- Li, H.Y., Zeng, W.L., Ye, Y.W., Chen, X., Zhang, M.M., Chen, Y.S., Liu, C.T., Zhong, Z.Q., Li, J., Wang, Y.
- ID
- ZDB-PUB-250703-13
- Date
- 2025
- Source
- American journal of physiology. Gastrointestinal and liver physiology : (Journal)
- Registered Authors
- Keywords
- Glia maturation factor-β, Hepatocyte-specific transgenic model, Metabolism-associated steatotic liver disease, Partial hepatectomy, Zebrafish
- MeSH Terms
-
- Animals, Genetically Modified
- Zebrafish
- STAT3 Transcription Factor/metabolism
- Disease Models, Animal
- Hepatocytes*/metabolism
- Hepatocytes*/pathology
- Animals
- Liver Regeneration*/physiology
- Hepatectomy
- Glia Maturation Factor*/genetics
- Glia Maturation Factor*/metabolism
- Fatty Liver*/genetics
- Fatty Liver*/metabolism
- Fatty Liver*/pathology
- Liver/metabolism
- Liver/pathology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Cell Proliferation
- PubMed
- 40602783 Full text @ Am. J. Physiol. Gastrointest. Liver Physiol.
Citation
Li, H.Y., Zeng, W.L., Ye, Y.W., Chen, X., Zhang, M.M., Chen, Y.S., Liu, C.T., Zhong, Z.Q., Li, J., Wang, Y. (2025) Glia maturation factor-β in hepatocytes enhances liver regeneration and mitigates steatosis and ballooning in zebrafish. American journal of physiology. Gastrointestinal and liver physiology. :.
Abstract
Glia maturation factor-β (Gmfb), an actin filament debrancher, was initially identified in brain and recently linked to liver diseases. To investigate the role of hepatocyte Gmfb (hep-Gmfb) in liver reparative regeneration, hepatocyte-specific gmfb knockout (HepGKO) and overexpression (HepGOE) zebrafish strains were constructed. Both transgenic and wild-type (WT) zebrafish underwent partial hepatectomy (PHX) or were fed high fat, high cholesterol diets to model metabolism-associated steatotic liver disease (MASLD). Under physiological conditions, the HepGKO, HepGOE, and WT fish displayed similar survival, gross appearance, and liver histology. Following PHX, WT liver gmfb levels positively correlated with cell proliferation and proinflammatory cytokine levels. HepGOE showed enhanced regeneration and reduced liver steatosis compared to WT, while HepGKO exhibited opposite effects. In MASLD, WT liver gmfb increased with disease progression. HepGKO experienced worsening liver enlargement, steatosis, ballooning, inflammation, and endoplasmic reticulum stress, while HepGOE showed improvements. HepGOE liver had the highest cell proliferation, but all three groups showed similar levels of cell apoptosis. Moreover, elevated proinflammatory cytokines were observed across MASLD groups, being the highest in HepGKO and lowest in HepGOE. However, stat3 activation was the lowest in HepGKO and highest in HepGOE, while jnk and mapk/erk activation was consistent across the MASLD groups. In il6-treated primary hepatocytes, gmfb abundance influenced stat3 activation, and hep-gmfb abundance significantly affected actin filaments distribution in hepatocytes both in vivo and vitro. Conclusions: Hep-Gmfb boosts regenerative processes by enhancing hepatocyte proliferation, alleviating fatty liver histological abnormalities, and modulating the Il6/Stat3 signaling, potentially through remodeling of actin-filament network within hepatocytes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping