The angiopoietin-like factor cornea-derived transcript 6 is a putative morphogen for human cornea
The angiopoietin-like factor cornea-derived transcript 6 is a putative morphogen for human cornea
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DOI：
10.1074/jbc.m105746200
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发表时间：
2002-01-04
影响因子：
4.8
通讯作者：
Westphal, JR
中科院分区：
文献类型：
--
作者：
Peek, R;Kammerer, RA;Westphal, JR
人角膜特异性蛋白角膜衍生转录本6（CDT6）是血管生成素基因家族的成员。我们报告CDT6的结构和功能表征。我们证明，CDT6是一种分泌蛋白，折叠成二硫键连接的同源四聚体卷曲螺旋相互作用。CDT6在无血管角膜基质层中以高水平表达的发现表明，该蛋白质类似于某些血管生成素，充当血管生成的负调节剂。为了检验这一假设并测定蛋白质对具有高血管密度的生长组织的作用，在小鼠异种移植模型中表达CDT6。CDT6的表达通过诱导大量纤维化导致肿瘤生长和异常血管形成的减少。有趣的是，CDT6的表达也导致了成熟角膜基质层典型的细胞外基质成分的沉积。这些观察结果强烈表明CDT6在体内诱导角膜表型中作为形态发生素的作用。
The human cornea-specific protein cornea-derived transcript 6 (CDT6) is a member of the angiopoietin gene family. We report the structural and functional characterization of CDT6. We demonstrate that CDT6 is a secreted protein that folds into disulfide-linked homotetramers by coiled-coil interactions. The finding that CDT6 is expressed at high levels in the avascular corneal stromal layer suggested that the protein, similar to certain angiopoietins, acts as a negative regulator of angiogenesis. To test this hypothesis and to assay the effect of the protein on a growing tissue with high vascular density, CDT6 was expressed in a mouse xenograft model. Expression of CDT6 led to a reduction in tumor growth and aberrant blood vessel formation by inducing massive fibrosis. Interestingly, expression of CDT6 also resulted in the deposition of extracellular matrix components typical for the mature corneal stromal layer. These observations strongly suggest a role as morphogen for CDT6 in inducing a corneal phenotype in vivo.