Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model

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 kras V12 ex...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Mohamed Helal, Chuan Yan, Zhiuyan Gong
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/0700a23680934a129bde399f453f74c5
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:0700a23680934a129bde399f453f74c5
record_format dspace
spelling oai:doaj.org-article:0700a23680934a129bde399f453f74c52021-12-02T15:23:00ZStimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model10.1038/s41598-020-80621-62045-2322https://doaj.org/article/0700a23680934a129bde399f453f74c52021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80621-6https://doaj.org/toc/2045-2322Abstract 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 kras V12 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.Mohamed HelalChuan YanZhiuyan GongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mohamed Helal
Chuan Yan
Zhiuyan Gong
Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model
description 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 kras V12 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.
format article
author Mohamed Helal
Chuan Yan
Zhiuyan Gong
author_facet Mohamed Helal
Chuan Yan
Zhiuyan Gong
author_sort Mohamed Helal
title Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model
title_short Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model
title_full Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model
title_fullStr Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model
title_full_unstemmed Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model
title_sort stimulation of hepatocarcinogenesis by activated cholangiocytes via il17a/f1 pathway in kras transgenic zebrafish model
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0700a23680934a129bde399f453f74c5
work_keys_str_mv AT mohamedhelal stimulationofhepatocarcinogenesisbyactivatedcholangiocytesviail17af1pathwayinkrastransgeniczebrafishmodel
AT chuanyan stimulationofhepatocarcinogenesisbyactivatedcholangiocytesviail17af1pathwayinkrastransgeniczebrafishmodel
AT zhiuyangong stimulationofhepatocarcinogenesisbyactivatedcholangiocytesviail17af1pathwayinkrastransgeniczebrafishmodel
_version_ 1718387306670325760