PUBLICATION
Progranulin A Promotes Compensatory Hepatocyte Proliferation via HGF/c-Met Signaling after Partial Hepatectomy in Zebrafish
- Authors
- Chiang, K.Y., Li, Y.W., Li, Y.H., Huang, S.J., Wu, C.L., Gong, H.Y., Wu, J.L.
- ID
- ZDB-PUB-211025-41
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(20): (Journal)
- Registered Authors
- Gong, Hong-Yi, Wu, Jen-Leih
- Keywords
- HGF, Vivo-Morpholino, c-met, cell cycle, cell proliferation, intraperitoneal injection, liver regeneration, partial hepatectomy, progranulin, zebrafish
- MeSH Terms
-
- Animals
- Cell Proliferation
- Hepatectomy/methods*
- Hepatocyte Growth Factor/genetics
- Hepatocyte Growth Factor/metabolism*
- Hepatocytes/cytology*
- Hepatocytes/metabolism
- Liver Regeneration*
- Organogenesis
- Progranulins/genetics
- Progranulins/metabolism*
- Proto-Oncogene Proteins c-met/genetics
- Proto-Oncogene Proteins c-met/metabolism*
- Signal Transduction
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34681875 Full text @ Int. J. Mol. Sci.
Citation
Chiang, K.Y., Li, Y.W., Li, Y.H., Huang, S.J., Wu, C.L., Gong, H.Y., Wu, J.L. (2021) Progranulin A Promotes Compensatory Hepatocyte Proliferation via HGF/c-Met Signaling after Partial Hepatectomy in Zebrafish. International Journal of Molecular Sciences. 22(20):.
Abstract
Compensatory hepatocyte proliferation and other liver regenerative processes are activated to sustain normal physiological function after liver injury. A major mitogen for liver regeneration is hepatocyte growth factor (HGF), and a previous study indicated that progranulin could modulate c-met, the receptor for HGF, to initiate hepatic outgrowth from hepatoblasts during embryonic development. However, a role for progranulin in compensatory hepatocyte proliferation has not been shown previously. Therefore, this study was undertaken to clarify whether progranulin plays a regulatory role during liver regeneration. To this end, we established a partial hepatectomy regeneration model in adult zebrafish that express a liver-specific fluorescent reporter. Using this model, we found that loss of progranulin A (GrnA) function by intraperitoneal-injection of a Vivo-Morpholino impaired and delayed liver regeneration after partial hepatectomy. Furthermore, transcriptome analysis and confirmatory quantitative real-time PCR suggested that cell cycle progression and cell proliferation was not as active in the morphants as controls, which may have been the result of comparative downregulation of the HGF/c-met axis by 36 h after partial hepatectomy. Finally, liver-specific overexpression of GrnA in transgenic zebrafish caused more abundant cell proliferation after partial hepatectomy compared to wild types. Thus, we conclude that GrnA positively regulates HGF/c-met signaling to promote hepatocyte proliferation during liver regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping