PUBLICATION
Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model
- Authors
- Helal, M., Yan, C., Gong, Z.
- ID
- ZDB-PUB-210116-5
- Date
- 2021
- Source
- Scientific Reports 11: 1372 (Journal)
- Registered Authors
- Gong, Zhiyuan
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Carcinogenesis*/genetics
- Carcinogenesis*/metabolism
- Hepatocytes/metabolism*
- Interleukin-17*/genetics
- Interleukin-17*/metabolism
- Liver Neoplasms, Experimental*/genetics
- Liver Neoplasms, Experimental*/metabolism
- Proto-Oncogene Proteins p21(ras)*/genetics
- Proto-Oncogene Proteins p21(ras)*/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 33446803 Full text @ Sci. Rep.
Citation
Helal, M., Yan, C., Gong, Z. (2021) Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model. Scientific Reports. 11:1372.
Abstract
It has been well known that tumor progression is dependent on secreted factors not only from tumor cells but also from other surrounding non-tumor cells. In the current study, we investigated the role of cholangiocytes during hepatocarcinogenesis following induction of oncogenic krasV12 expression in hepatocytes using an inducible transgenic zebrafish model. Upon induction of carcinogenesis in hepatocytes, a progressive cell proliferation in cholangiocytes was observed. The proliferative response in cholangiocytes was induced by enhanced lipogenesis and bile acids secretion from hepatocytes through activation of Sphingosine 1 phosphate receptor 2 (S1pr2), a known cholangiocyte receptor involving in cholangiocyte proliferation. Enhancement and inhibition of S1pr2 could accelerate or inhibit cholangiocyte proliferation and hepatocarcinogenesis respectively. Gene expression analysis of hepatocytes and cholangiocytes showed that cholangiocytes stimulated carcinogenesis in hepatocytes via an inflammatory cytokine, Il17a/f1, which activated its receptor (Il17ra1a) on hepatocytes and enhanced hepatocarcinogenesis via an ERK dependent pathway. Thus, the enhancing effect of cholangiocytes on hepatocarcinogenesis is likely via an inflammatory loop.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping