Roles of lumican and keratocan on corneal transparency
Roles of lumican and keratocan on corneal transparency
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DOI：
10.1023/a:1025396316169
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发表时间：
2002-05-01
影响因子：
3
通讯作者：
Liu, CY
中科院分区：
文献类型：
--
作者：
Kao, WWY;Liu, CY
Lumican和keratocan是小的富含亮氨酸的蛋白聚糖（SLRP）家族的成员，并且是角膜基质中主要的硫酸角质素（KS）蛋白聚糖。Lumican和Keratocan对于胚胎发育期间的正常角膜形态发生和成人角膜地形图的维持都是必不可少的。这归因于它们的双功能特性（结合胶原原纤维以调节胶原原纤维直径的蛋白质部分，以及延伸出来以调节原纤维间间距的高电荷糖胺聚糖（GAG）链），这有助于它们在细胞外基质组装中的调节作用。由于胶原基质的改变，光蛋白聚糖的缺乏导致纯合基因敲除小鼠角膜混浊的形成，其特征在于更大的原纤维直径和混乱的原纤维间距。相比之下，角膜蛋白聚糖敲除小鼠表现出薄但透明的角膜，基质胶原生成基质的变化微不足道。角膜蛋白聚糖的突变导致人类角膜扁平，常与青光眼相关。这些观察结果表明，Lumican和keratocan在调节基质细胞外基质的形成中具有不同的作用。实验证据表明，Lumican可能具有额外的生物学功能，如在伤口愈合和肿瘤发生中调节细胞迁移和上皮-间充质转变，以及调节胶原纤维生成。
Lumican and keratocan are members of the small leucine-rich proteoglycan (SLRP) family, and are the major keratan sulfate (KS) proteoglycans in corneal stroma. Both lumican and keratocan are essential for normal cornea morphogenesis during embryonic development and maintenance of corneal topography in adults. This is attributed to their bi-functional characteristic (protein moiety binding collagen fibrils to regulate collagen fibril diameters, and highly charged glycosaminoglycan (GAG) chains extending out to regulate interfibrillar spacings) that contributes to their regulatory role in extracellular matrix assembly. The absence of lumican leads to formation of cloudy corneas in homozygous knockout mice due to altered collagenous matrix characterized by larger fibril diameters and disorganized fibril spacing. In contrast, keratocan knockout mice exhibit thin but clear cornea with insignificant alteration of stromal collaegenous matrix. Mutations of keratocan cause cornea plana in human, which is often associated with glaucoma. These observations suggest that lumican and keratocan have different roles in regulating formation of stromal extracellular matrix. Experimental evidence indicates that lumican may have additional biological functions, such as modulation of cell migration and epithelium-mesenchyme transition in wound healing and tumorgenesis, besides regulating collagen fibrillogenesis.