Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-26612-0
Title: Interaction of hepatic stellate cells with neutrophils and macrophages in the liver following oncogenic kras activation in transgenic zebrafish
Authors: Yang, Q 
Yan, C 
Gong, Z 
Keywords: indole derivative
N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea
protein p21
serotonin
serotonin 2B receptor
transforming growth factor beta1
urea
zebrafish protein
animal
cytology
drug effect
genetics
hepatic stellate cell
liver
liver cell
liver tumor
macrophage
metabolism
neutrophil
pathology
signal transduction
transgenic animal
tumor microenvironment
upregulation
veterinary medicine
zebra fish
Animals
Animals, Genetically Modified
Hepatic Stellate Cells
Hepatocytes
Indoles
Liver
Liver Neoplasms
Macrophages
Neutrophils
Proto-Oncogene Proteins p21(ras)
Receptor, Serotonin, 5-HT2B
Serotonin
Signal Transduction
Transforming Growth Factor beta1
Tumor Microenvironment
Up-Regulation
Urea
Zebrafish
Zebrafish Proteins
Issue Date: 2018
Citation: Yang, Q, Yan, C, Gong, Z (2018). Interaction of hepatic stellate cells with neutrophils and macrophages in the liver following oncogenic kras activation in transgenic zebrafish. Scientific Reports 8 (1) : 8495. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-26612-0
Abstract: Activation of hepatic stellate cells (HSC) plays a crucial role in the liver disease progression from liver fibrosis/cirrhosis to cancer. Here, we found a rapid change of microenvironment after kras V12 -induction in zebrafish liver with progressively increased stromal cell number and enlarged liver size. Neutrophils and macrophages exhibited a faster response than HSCs. By manipulating the numbers of neutrophils and macrophages through morpholino knockdown, we found that macrophages contributed to both HSC survival and activation while neutrophils appear to be only required for HSC activation. Serotonin, which is essential for HSC survival and activation, was found up-regulated in hepatocytes and macrophages, but not in neutrophils after kras V12 induction. Serotonin receptor was highly expressed in HSCs; increase of the receptor activity by an agonist stimulated HSCs and oncogenic growth of the liver while an opposite effect was observed with an antagonist. Activated HSCs promoted the pro-tumorigenesis functions of neutrophils and macrophages through secretion of Tgfb1. Overall, these observations elucidated a cellular interaction in microenvironment where that upregulated serotonin in hepatocytes and macrophages activated HSCs. Since the microenvironment crosstalk plays a vital role in manipulation of liver carcinogenesis, the underlying mechanism may provide potential therapeutic targets for liver diseases. © 2018 The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/175020
ISSN: 20452322
DOI: 10.1038/s41598-018-26612-0
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