Small peptides derived from somatotropin domain-containing proteins inhibit blood and lymphatic endothelial cell proliferation, migration, adhesion and tube formation
Small peptides derived from somatotropin domain-containing proteins inhibit blood and lymphatic endothelial cell proliferation, migration, adhesion and tube formation
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DOI：
10.1016/j.biocel.2011.08.020
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发表时间：
2011-12-01
影响因子：
4
通讯作者：
Popel, Aleksander S.
中科院分区：
文献类型：
--
作者：
Lee, Esak;Rosca, Elena V.;Popel, Aleksander S.
血管生成在健康中是完全平衡和调节的;然而，它在许多疾病中失调，包括癌症、年龄相关性黄斑变性、心血管疾病如冠状动脉和外周动脉疾病和中风、异常胚胎发育和异常伤口愈合。除了血管生成，淋巴管生成对于维持免疫系统、体液和淋巴器官的稳态是关键的;失调的淋巴管生成可引起炎性疾病和淋巴结介导的肿瘤转移。抗血管生成或抗淋巴管生成小肽可作为使疾病状况中的血管生成或淋巴管生成正常化的治疗剂发挥重要作用。几个新的内源性肽衍生自含有保守的生长激素结构域的蛋白质先前已确定与我们的生物信息学为基础的方法的帮助下。使用血液和淋巴管内皮细胞的体外增殖、迁移、粘附和管形成测定筛选这些生长激素肽抑制血管生成和淋巴管生成。我们发现这些肽具有抑制血管生成和淋巴管生成的潜力。针对淋巴管生成抑制的研究，我们发现来自人跨膜蛋白45 A的生长激素保守结构域的肽是最有效的淋巴管生成抑制剂，阻断淋巴管内皮细胞迁移、粘附和管形成。(C)2011爱思唯尔有限公司版权所有。
Angiogenesis is thoroughly balanced and regulated in health; however, it is dysregulated in many diseases including cancer, age-related macular degeneration, cardiovascular diseases such as coronary and peripheral artery diseases and stroke, abnormal embryonic development, and abnormal wound healing. In addition to angiogenesis, lymphangiogenesis is pivotal for maintaining the immune system, homeostasis of body fluids and lymphoid organs; dysregulated lymphangiogenesis may cause inflammatory diseases and lymph node mediated tumor metastasis. Anti-angiogenic or anti-lymphangiogenic small peptides may play an important role as therapeutic agents normalizing angiogenesis or lymphangiogenesis in disease conditions. Several novel endogenous peptides derived from proteins containing a conserved somatotropin domain have been previously identified with the help of our bioinformatics-based methodology. These somatotropin peptides were screened for inhibition of angiogenesis and lymphangiogenesis using in vitro proliferation, migration, adhesion and tube formation assays with blood and lymphatic endothelial cells. We found that the peptides have the potential for inhibiting both angiogenesis and lymphangiogenesis. Focusing the study on the inhibition of lymphangiogenesis, we found that a peptide derived from the somatotropin conserved domain of transmembrane protein 45A human was the most potent lymphangiogenesis inhibitor, blocking lymphatic endothelial cell migration, adhesion, and tube formation. (C) 2011 Elsevier Ltd. All rights reserved.