Knockout of Factor-Inhibiting HIF ( Hif1an ) in Colon Epithelium Attenuates Chronic Colitis but Does Not Reduce Colorectal Cancer in Mice.

Autor:	Schützhold V; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany., Gravemeyer J; Translational Skin Cancer Research, Dermatologie, Universitätsmedizin Essen, Essen, Germany.; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany., Bicker A; Molekulargenetik und Genomanalyse, Institut für Organismische und Molekulare Evolutionsbiologie, Johannes Gutenberg-Universität Mainz, Mainz, Germany; and., Hager T; Institut für Pathologie, Universität Duisburg-Essen, Essen, Germany., Padberg C; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany., Schäfer J; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany., Wrobeln A; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany., Steinbrink M; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany., Zeynel S; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany., Hankeln T; Molekulargenetik und Genomanalyse, Institut für Organismische und Molekulare Evolutionsbiologie, Johannes Gutenberg-Universität Mainz, Mainz, Germany; and., Becker JC; Translational Skin Cancer Research, Dermatologie, Universitätsmedizin Essen, Essen, Germany.; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany., Fandrey J; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany; joachim.fandrey@uni-due.de., Winning S; Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 Mar 01; Vol. 208 (5), pp. 1280-1291. Date of Electronic Publication: 2022 Feb 04.
DOI:	10.4049/jimmunol.2100418
Abstrakt:	Inflammatory bowel disease such as chronic colitis promotes colorectal cancer, which is a common cause of cancer mortality worldwide. Hypoxia is a characteristic of inflammation as well as of solid tumors and enforces a gene expression response controlled by hypoxia-inducible factors (HIFs). Once established, solid tumors are immunosuppressive to escape their abatement through immune cells. Although HIF activity is known to 1) promote cancer development and 2) drive tumor immune suppression through the secretion of adenosine, both prolyl hydroxylases and an asparaginyl hydroxylase termed factor-inhibiting HIF (FIH) negatively regulate HIF. Thus, FIH may act as a tumor suppressor in colorectal cancer development. In this study, we examined the role of colon epithelial FIH in a mouse model of colitis-induced colorectal cancer. We recapitulated colitis-associated colorectal cancer development in mice using the azoxymethane/dextran sodium sulfate model in Vil1-Cre/FIH +f/+f and wild-type siblings. Colon samples were analyzed regarding RNA and protein expression and histology. Vil1-Cre/FIH +f/+f mice showed a less severe colitis progress compared with FIH +f/+f animals and a lower number of infiltrating macrophages in the inflamed tissue. RNA sequencing analyses of colon tissue revealed a lower expression of genes associated with the immune response in Vil1-Cre/FIH +f/+f mice. However, tumor occurrence did not significantly differ between Vil1-Cre/FIH +f/+f and wild-type mice. Thus, FIH knockout in colon epithelial cells did not modulate colorectal cancer development but reduced the inflammatory response in chronic colitis. (Copyright © 2022 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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