Nod2 protects mice from inflammation and obesity-dependent liver cancer

Abstract Nod2 is a pattern recognition receptor that modulates host innate immune responses and protects from inflammation, steatosis, and obesity. Obesity and inflammation are risk factors for hepatocellular carcinoma, however, the role of Nod2 in obesity-dependent hepatic tumorigenesis is not know...

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Autores principales:	Serdar A. Gurses, Sunil Banskar, Cody Stewart, Bill Trimoski, Roman Dziarski, Dipika Gupta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/717b3f606c254c97af41ede6ebd03a0e
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spelling	oai:doaj.org-article:717b3f606c254c97af41ede6ebd03a0e2021-12-02T15:10:10ZNod2 protects mice from inflammation and obesity-dependent liver cancer10.1038/s41598-020-77463-72045-2322https://doaj.org/article/717b3f606c254c97af41ede6ebd03a0e2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77463-7https://doaj.org/toc/2045-2322Abstract Nod2 is a pattern recognition receptor that modulates host innate immune responses and protects from inflammation, steatosis, and obesity. Obesity and inflammation are risk factors for hepatocellular carcinoma, however, the role of Nod2 in obesity-dependent hepatic tumorigenesis is not known. Here we tested the hypothesis that Nod2 protects from high fat diet (HFD)-dependent hepatic cancer. We used an obesity-dependent hepatic tumor model. WT and Nod2 −/− mice were treated with the carcinogen dimethylbenz[a]anthracene (DMBA) and maintained on HFD. Nod2 −/− mice treated with DMBA and maintained on HFD gain significantly more weight and develop more liver tumors than similarly treated WT mice. Livers of Nod2 −/− tumorigenic mice had increased expression of genes involved in cell proliferation, immune responses, and cholesterol biosynthesis, increased infiltration of neutrophils, inflammatory monocytes, and T cells, and increased activation of STAT3 and ERK during the later stages of tumorigenesis. Bioinformatic analyses of genes with differential expression predicted an increase in cancer, immune, and cholesterol biosynthesis pathways. In summary, we have identified a novel role for Nod2 and demonstrate that Nod2 protects from HFD-dependent liver malignancy and this protection is accompanied by decreased cell proliferation, inflammation, steroid biosynthesis, neutrophils and macrophages infiltration, and STAT3 and MAPK signaling in the liver.Serdar A. GursesSunil BanskarCody StewartBill TrimoskiRoman DziarskiDipika GuptaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Serdar A. Gurses Sunil Banskar Cody Stewart Bill Trimoski Roman Dziarski Dipika Gupta Nod2 protects mice from inflammation and obesity-dependent liver cancer
description	Abstract Nod2 is a pattern recognition receptor that modulates host innate immune responses and protects from inflammation, steatosis, and obesity. Obesity and inflammation are risk factors for hepatocellular carcinoma, however, the role of Nod2 in obesity-dependent hepatic tumorigenesis is not known. Here we tested the hypothesis that Nod2 protects from high fat diet (HFD)-dependent hepatic cancer. We used an obesity-dependent hepatic tumor model. WT and Nod2 −/− mice were treated with the carcinogen dimethylbenz[a]anthracene (DMBA) and maintained on HFD. Nod2 −/− mice treated with DMBA and maintained on HFD gain significantly more weight and develop more liver tumors than similarly treated WT mice. Livers of Nod2 −/− tumorigenic mice had increased expression of genes involved in cell proliferation, immune responses, and cholesterol biosynthesis, increased infiltration of neutrophils, inflammatory monocytes, and T cells, and increased activation of STAT3 and ERK during the later stages of tumorigenesis. Bioinformatic analyses of genes with differential expression predicted an increase in cancer, immune, and cholesterol biosynthesis pathways. In summary, we have identified a novel role for Nod2 and demonstrate that Nod2 protects from HFD-dependent liver malignancy and this protection is accompanied by decreased cell proliferation, inflammation, steroid biosynthesis, neutrophils and macrophages infiltration, and STAT3 and MAPK signaling in the liver.
format	article
author	Serdar A. Gurses Sunil Banskar Cody Stewart Bill Trimoski Roman Dziarski Dipika Gupta
author_facet	Serdar A. Gurses Sunil Banskar Cody Stewart Bill Trimoski Roman Dziarski Dipika Gupta
author_sort	Serdar A. Gurses
title	Nod2 protects mice from inflammation and obesity-dependent liver cancer
title_short	Nod2 protects mice from inflammation and obesity-dependent liver cancer
title_full	Nod2 protects mice from inflammation and obesity-dependent liver cancer
title_fullStr	Nod2 protects mice from inflammation and obesity-dependent liver cancer
title_full_unstemmed	Nod2 protects mice from inflammation and obesity-dependent liver cancer
title_sort	nod2 protects mice from inflammation and obesity-dependent liver cancer
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/717b3f606c254c97af41ede6ebd03a0e
work_keys_str_mv	AT serdaragurses nod2protectsmicefrominflammationandobesitydependentlivercancer AT sunilbanskar nod2protectsmicefrominflammationandobesitydependentlivercancer AT codystewart nod2protectsmicefrominflammationandobesitydependentlivercancer AT billtrimoski nod2protectsmicefrominflammationandobesitydependentlivercancer AT romandziarski nod2protectsmicefrominflammationandobesitydependentlivercancer AT dipikagupta nod2protectsmicefrominflammationandobesitydependentlivercancer
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Nod2 protects mice from inflammation and obesity-dependent liver cancer

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