Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases.
Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases.
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DOI：
10.1111/j.1582-4934.2010.01146.x
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发表时间：
2011-07
影响因子：
5.3
通讯作者：
Naschberger E
中科院分区：
文献类型：
--
作者：
Hammon M;Herrmann M;Bleiziffer O;Pryymachuk G;Andreoli L;Munoz LE;Amann KU;Mondini M;Gariglio M;Airó P;Schellerer VS;Hatzopoulos AK;Horch RE;Kneser U;Stürzl M;Naschberger E
风湿性自身免疫性疾病的特征在于与内皮祖细胞（EPC）功能受损和伴随的血管缺陷相关的持续促炎微环境。鸟苷酸结合蛋白-1（GBP-1）是一种由多种促炎细胞因子诱导的抑制内皮细胞增殖、迁移和侵袭的标志物和细胞内调节因子。此外，GBP-1由内皮细胞主动分泌。在这项研究中，在慢性炎症性疾病患者的血清中检测到GBP-1水平显著升高。因此，我们研究了GBP-1在EPC中的功能。有趣的是，GBP-1在T17 b EPC中的稳定表达诱导了这些细胞的过早分化，如Flk-1和von Willebrand因子表达的稳健上调所示。此外，GBP-1在体外可抑制EPC的增殖和迁移。我们证实，GBP-1抑制血管定向迁移的EPC在组织水平上使用大鼠动静脉环模型作为一种新的定量体内迁移试验。总体而言，我们的研究结果表明，GBP-1有助于血管功能障碍的慢性炎症性疾病，通过抑制EPC血管生成活性诱导过早的EPC分化。
Rheumatic autoimmune disorders are characterized by a sustained pro-inflammatory microenvironment associated with impaired function of endothelial progenitor cells (EPC) and concomitant vascular defects. Guanylate binding protein-1 (GBP-1) is a marker and intracellular regulator of the inhibition of proliferation, migration and invasion of endothelial cells induced by several pro-inflammatory cytokines. In addition, GBP-1 is actively secreted by endothelial cells. In this study, significantly increased levels of GBP-1 were detected in the sera of patients with chronic inflammatory disorders. Accordingly we investigated the function of GBP-1 in EPC. Interestingly, stable expression of GBP-1 in T17b EPC induced premature differentiation of these cells, as indicated by a robust up-regulation of both Flk-1 and von Willebrand factor expression. In addition, GBP-1 inhibited the proliferation and migration of EPC in vitro. We confirmed that GBP-1 inhibited vessel-directed migration of EPC at the tissue level using the rat arterio-venous loop model as a novel quantitative in vivo migration assay. Overall, our findings indicate that GBP-1 contributes to vascular dysfunction in chronic inflammatory diseases by inhibiting EPC angiogenic activity via the induction of premature EPC differentiation.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
--
作者：
Kuwana, Masataka;Kaburaki, Junichi;Ikeda, Yasuo
通讯作者：
Ikeda, Yasuo
影响因子：
6
作者：
Lubeseder-Martellato, C;Guenzi, E;Stürzl, M
通讯作者：
Stürzl, M
影响因子：
5.3
作者：
Arkudas A;Tjiawi J;Saumweber A;Beier JP;Polykandriotis E;Bleiziffer O;Horch RE;Kneser U
通讯作者：
Kneser U
影响因子：
9.8
作者：
Decaris, Martin L.;Lee, Chang I.;Yoder, Mervin C.;Tarantal, Alice F.;Leach, J. Kent
通讯作者：
Leach, J. Kent