Oulu Center for Cell-Matrix Research, Biocenter and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland
Matrix Biol. 2011 Mar;30(2):83-92. doi: 10.1016/j.matbio.2010.11.001. Epub 2010 Dec 14.
Collagen XVIII is a heparan sulphate proteoglycan which is expressed ubiquitously in different basement membranes throughout the body. Its C-terminal fragment, endostatin, has been found to inhibit angiogenesis and tumor growth by restricting endothelial proliferation and migration and inducing apoptosis of endothelial cells. Collagen XVIII has three variants, of which the shortest one is found in most vascular and epithelial BM structures, whereas the longer variants are found especially in the liver. The longest or frizzled variant has a cysteine-rich domain in its N-terminus that has been shown to inhibit Wnt signaling in vitro. The presence of collagen XVIII homologues in organisms such as C. elegans, Xenopus laevis, zebrafish and chick suggests a fundamental role for this BM collagen. Mutations in the collagen XVIII gene lead to the Knobloch syndrome, which is characterized by high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele. Mice lacking collagen XVIII also show several ocular abnormalities. This suggests that in physiological conditions collagen XVIII is mostly needed for the proper development of the eye. Moreover, it appears to be needed for the structural stability of basement membranes in several other organs, and increasing evidence shows its importance for other organs in non-physiological situations such as atherosclerosis, glomerulonephritis or other type of tissue damage. This review focuses on clarifying the roles of collagen XVIII and its variants and domains in various physiological and pathological conditions.
XVIII 型胶原是一种硫酸乙酰肝素蛋白聚糖，在体内各种基底膜中广泛表达。其 C 端片段内皮抑素被发现通过限制内皮细胞增殖和迁移并诱导内皮细胞凋亡来抑制血管生成和肿瘤生长。XVIII 型胶原有三种变体，其中最短的一种存在于大多数血管和上皮 BM 结构中，而较长的变体则特别存在于肝脏中。最长或卷曲的变体在其 N 端具有富含半胱氨酸的结构域，已被证明在体外抑制 Wnt 信号通路。在秀丽隐杆线虫、非洲爪蟾、斑马鱼和鸡等生物中存在 XVIII 型胶原同源物，表明这种 BM 胶原具有重要的基本作用。XVIII 型胶原基因突变导致 Knobloch 综合征，其特征是高度近视、玻璃体视网膜变性伴视网膜脱离、黄斑异常和枕骨脑膨出。缺乏 XVIII 型胶原的小鼠也表现出多种眼部异常。这表明在生理条件下，XVIII 型胶原主要用于眼睛的正常发育。此外，它似乎对于其他器官基底膜的结构稳定性也是必需的，越来越多的证据表明，在非生理情况下，如动脉粥样硬化、肾小球肾炎或其他类型的组织损伤，它对其他器官也很重要。这篇综述重点阐明了 XVIII 型胶原及其变体和结构域在各种生理和病理条件下的作用。
