Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen
Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen
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DOI：
10.1016/j.febslet.2005.05.043
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发表时间：
2005-07-04
期刊：
影响因子：
3.5
通讯作者：
Azar, DT
中科院分区：
文献类型：
--
作者：
Chang, JH;Javier, JAD;Azar, DT
几种抗血管生成因子来源于大分子的蛋白水解加工，包括来自XVIII型胶原的内皮抑制素和来自纤溶酶原的血管抑制素。在以前的研究中，我们表明，新抑素-7，C-末端28 kDa内皮抑制素跨越蛋白水解片段，是由基质金属蛋白酶基质溶解素（MMP）-7对XVIII型胶原蛋白的蛋白水解作用产生的。现在，我们报告了新抑素蛋白质家族的第二个成员，新抑素-14。由于天然存在的胶原蛋白XVIII分解产生少量的新他汀-7和-14（分别使用MMP-7和-14），我们使用另外两种方法来表征这些分子的抗血管生成特性：体外鼠重组新他汀和基因治疗。我们证明，小鼠重组新抑素-7抑制小牛肺动脉内皮细胞增殖和微量注射新抑素-7和新抑素-14裸DNA到小鼠角膜基质中的结果显着减少碱性成纤维细胞生长因子诱导的角膜新生血管。这些结果为新他汀类药物可能的抗血管生成作用提供了支持性证据。(c)2005年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Several anti-angiogenic factors are derived from proteolytic processing of large molecules including endostatin from type XVIII collagen and angiostatin from plasminogen. In previous studies we showed that neostatin-7, the C-terminal 28 kDa endostatin-spanning proteolytic fragment, is generated from the proteolytic action of matrix metalloproteinase matrilysin (MMP)-7 on type XVIII collagen. Now, we report a second member of the neostatin family of proteins, neostatin-14. Given the small quantities of neostatin-7 and -14 generated by the breakdown of naturally occurring collagen XVIII (using MMP-7 and -14, respectively), we used two other approaches to characterize the anti-angiogenic properties of these molecules: murine recombinant neostatin in vitro, and gene therapy. We demonstrate that murine recombinant neostatin-7 inhibits calf pulmonary artery endothelial cell proliferation and that microinjection of neostatin-7 and neostatin-14 naked DNA into the corneal stroma of mice results in significant reduction of basic fibroblast growth factor-induced corneal neovascularization. These results provide supportive evidence of the possible antiangiogenic effect of neostatins. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.