Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases
Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases
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DOI：
10.3748/wjg.v22.i28.6434
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发表时间：
2016-07-28
影响因子：
4.3
通讯作者：
Stuerzl, Michael
中科院分区：
文献类型：
--
作者：
Britzen-Laurent, Nathalie;Herrmann, Christian;Stuerzl, Michael
鸟苷酸结合蛋白（GBP）是干扰素刺激的因子，参与防御细胞病原体和炎症。这些蛋白质，特别是GBP-1，家族中最突出的成员，已被确定为各种疾病中干扰素-γ激活细胞的可靠标志物，包括结直肠癌（CRC）和炎症性肠病（IBD）。在CRC中，GBP-1表达与Th 1主导的血管抑制微环境相关，并与更好的结局相关。GBP-1对肿瘤生长的抑制是其强的抗血管生成活性以及其对肿瘤细胞的直接抗肿瘤作用的结果。在IBD中，GBP-1介导干扰素-γ对肠上皮细胞的抗增殖作用。此外，它通过防止细胞凋亡、抑制血管生成和调节T细胞受体信号传导对粘膜起保护作用。这些功能在很大程度上依赖于GBP-1与肌动蛋白细胞骨架相互作用和重塑的能力。
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-gamma-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-gamma 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.