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World J Gastroenterol. Jul 28, 2016; 22(28): 6434-6443
Published online Jul 28, 2016. doi: 10.3748/wjg.v22.i28.6434
Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases
Nathalie Britzen-Laurent, Christian Herrmann, Elisabeth Naschberger, Roland S Croner, Michael Stürzl
Nathalie Britzen-Laurent, Elisabeth Naschberger, Michael Stürzl, Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Translational Research Center, Friedrich-Alexander University of Erlangen-Nuremberg, 91054 Erlangen, Germany
Christian Herrmann, Physical Chemistry I, Ruhr-University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany
Roland S Croner, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, 91054 Erlangen, Germany
Author contributions: Britzen-Laurent N, Herrmann C, Naschberger E, Croner RS and Stürzl M performed the literature analysis, discussed the data and contributed to the assembly of the manuscript; Britzen-Laurent N and Stürzl M wrote the manuscript.
Supported by German Research Foundation, No. DFG-KFO257 (sub-project 4), No. DFG-BR5196 and No. SFB796 (sub-project B9); Interdisciplinary Center for Clinical Research (IZKF) of the Clinical Center Erlangen.
Conflict-of-interest statement: The authors declare having no conflict-of-interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Michael Stürzl, Professor, Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Translational Research Center, Friedrich-Alexander University of Erlangen-Nuremberg, Schwabachanlage 12, 91054 Erlangen, Germany. michael.stuerzl@uk-erlangen.de
Telephone: +49-913185-39520 Fax: +49-913185-39523
Received: April 4, 2016
Peer-review started: April 5, 2016
First decision: May 12, 2016
Revised: May 25, 2016
Accepted: June 13, 2016
Article in press: June 13, 2016
Published online: July 28, 2016
Processing time: 108 Days and 18.2 Hours
Abstract

Guanylate-binding proteins (GBPs) are interferon-stimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma (CRC) and inflammatory bowel diseases (IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong anti-angiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.

Keywords: Guanylate-binding proteins; Colorectal carcinoma; Inflammatory bowel diseases; Interferon

Core tip: Guanylate-binding proteins (GBPs) are interferon-stimulated factors involved in the defense against cellular pathogens and inflammation. In addition, guanylate-binding proteins have been established as reliable markers of interferon-γ-activated cells in various diseases including colorectal carcinoma and inflammatory bowel diseases. The GBP-1 is the best characterized member of the family. For instance, the expression of GBP-1 has been associated with a better outcome in colorectal carcinoma. The inhibition of tumor growth by GBP-1 is due to its strong anti-angiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In inflammatory bowel diseases, on the one hand GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells, and on the other hand, it protects the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.