Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases.
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.
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.
Nathalie
N
Britzen-Laurent
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
C
Herrmann
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.
Elisabeth
E
Naschberger
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.
Roland S
RS
Croner
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.
Michael
M
Stürzl
D017209:Apoptosis / Q000276:immunology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
C490287:GBP1 protein, human; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D019204:GTP-Binding Proteins
Colorectal carcinoma; Guanylate-binding proteins; Inflammatory bowel diseases; Interferon