Baird A, Esch F, Gospodarowicz D, Guillemin R
Biochemistry. 1985 Dec 31;24(27):7855-60. doi: 10.1021/bi00348a001.
Two retina-derived growth factors have been isolated on the basis of their ability to stimulate the proliferation of capillary endothelial cells in vitro. Gas-phase sequence analysis identified the amino-terminal sequence of the major form of the mitogen as being identical with residues 1-35 of bovine basic fibroblast growth factor (FGF). Amino-terminal sequence analysis of the second form identified 28 residues that are indistinguishable from those of brain acidic FGF (residues 1-28). The possibility that these retina-derived endothelial cell growth factors are related to, if not identical with, basic and acidic FGF is supported by observations that they have similar molecular weights (15000-16000), similar retention behavior on all steps of chromatography (ion-exchange, heparin-Sepharose), and similar amino acid compositions and that they cross-react with antibodies to basic and acidic FGF. The eye-derived growth factors, like FGF, are potent stimulators of capillary endothelial cell growth in vitro. The results identify the major retina-derived endothelial cell growth factor as indistinguishable from basic FGF and demonstrate the presence of an acidic FGF in the eye. They suggest that at least some of the mitogenic, angiogenic, and neovascularizing activities described as being present in the retina are due to the existence of FGF in this tissue. The implications of this finding on the etiology and pathophysiology of vasoproliferative diseases of the eye are discussed.
基于两种视网膜衍生生长因子在体外刺激毛细血管内皮细胞增殖的能力,它们已被分离出来。气相序列分析确定,有丝分裂原主要形式的氨基末端序列与牛碱性成纤维细胞生长因子(FGF)的1 - 35位残基相同。对第二种形式的氨基末端序列分析确定了28个与脑酸性FGF(1 - 28位残基)无法区分的残基。这些视网膜衍生的内皮细胞生长因子即使与碱性和酸性FGF不完全相同,也与之相关,这一可能性得到了以下观察结果的支持:它们具有相似的分子量(15000 - 16000)、在色谱分析的所有步骤(离子交换、肝素 - 琼脂糖)中具有相似的保留行为、相似的氨基酸组成,并且它们与针对碱性和酸性FGF的抗体发生交叉反应。眼源性生长因子与FGF一样,是体外毛细血管内皮细胞生长的有效刺激剂。结果表明,主要的视网膜衍生内皮细胞生长因子与碱性FGF无法区分,并证明眼中存在酸性FGF。它们表明,视网膜中描述的至少一些促有丝分裂、血管生成和新生血管形成活性是由于该组织中存在FGF。本文讨论了这一发现对眼部血管增殖性疾病的病因学和病理生理学的影响。