PUBLICATION
Sex disparity in zebrafish liver cell proliferation after partial hepatectomy is regulated by sex hormone receptors and the S100A1-YAP signaling cascade
- Authors
- Zhu, M., Li, Y., Shen, Q., Gong, Z., Liu, D.
- ID
- ZDB-PUB-241014-9
- Date
- 2024
- Source
- Disease models & mechanisms 17(10): (Journal)
- Registered Authors
- Gong, Zhiyuan
- Keywords
- Liver Regeneration, Partial Hepatectomy, Sex Disparity, Zebrafish
- MeSH Terms
-
- YAP-Signaling Proteins*
- Receptors, Androgen/metabolism
- Cell Proliferation*
- Zebrafish*/metabolism
- Receptors, Estrogen/metabolism
- Sex Characteristics
- Signal Transduction*
- Calcium-Binding Proteins/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Hepatocytes*/metabolism
- Male
- Animals
- Hepatectomy*
- Adaptor Proteins, Signal Transducing/metabolism
- Liver*/metabolism
- Liver*/pathology
- S100 Proteins/metabolism
- Liver Regeneration*
- Female
- PubMed
- 39397390 Full text @ Dis. Model. Mech.
Citation
Zhu, M., Li, Y., Shen, Q., Gong, Z., Liu, D. (2024) Sex disparity in zebrafish liver cell proliferation after partial hepatectomy is regulated by sex hormone receptors and the S100A1-YAP signaling cascade. Disease models & mechanisms. 17(10):.
Abstract
Partial hepatectomy (PH) is commonly practiced to treat patients with hepatocellular carcinoma. The recovery of patients from PH depends on the proper initiation of liver regeneration, a process that mainly relies on liver cell proliferation. As sex affects human liver regeneration progress, we investigated how the sex disparity is achieved in PH-induced liver regeneration of adult zebrafish. We found that males began liver regeneration earlier than females after PH in terms of liver cell proliferation and liver mass recovery. This sex disparity was associated with an earlier activation of YAP signaling in male livers. We also found that androgen receptors regulate the sex-biased liver regeneration in a YAP-dependent manner and activated estrogen receptors are responsible for the later onset of female hepatocyte proliferation. Furthermore, a calcium-binding protein, S100A1, was identified to regulate the sex disparity of liver regeneration, as heterozygous S100A1 knockout inhibited YAP activity in male livers and delayed hepatocyte proliferation in males following PH. Therefore, the current study indicates that multiple pathways and/or their interplays contribute to the sex disparity of liver regeneration. Our findings suggest that fine-formulated and sex-biased therapeutic strategies are required to help patients who have received PH-based therapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping