Heparan sulfate proteoglycans (HSPGs) of the ocular lens

IF 18.6 1区 医学 Q1 OPHTHALMOLOGY Progress in Retinal and Eye Research Pub Date : 2023-03-01 DOI:10.1016/j.preteyeres.2022.101118
Tayler F.L. Wishart , Frank J. Lovicu
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引用次数: 4

Abstract

Heparan sulfate proteoglycans (HSPGs) reside in most cells; on their surface, in the pericellular milieu and/or extracellular matrix. In the eye, HSPGs can orchestrate the activity of key signalling molecules found in the ocular environment that promote its development and homeostasis. To date, our understanding of the specific roles played by individual HSPG family members, and the heterogeneity of their associated sulfated HS chains, is in its infancy. The crystalline lens is a relatively simple and well characterised ocular tissue that provides an ideal stage to showcase and model the expression and unique roles of individual HSPGs. Individual HSPG core proteins are differentially localised to eye tissues in a temporal and spatial developmental- and cell-type specific manner, and their loss or functional disruption results in unique phenotypic outcomes for the lens, and other ocular tissues. More recent work has found that different HS sulfation enzymes are also presented in a cell- and tissue-specific manner, and that disruption of these different sulfation patterns affects specific HS-protein interactions. Not surprisingly, these sulfated HS chains have also been reported to be required for lens and eye development, with dysregulation of HS chain structure and function leading to pathogenesis and eye-related phenotypes. In the lens, HSPGs undergo significant and specific changes in expression and function that can drive pathology, or in some cases, promote tissue repair. As master signalling regulators, HSPGs may one day serve as valuable biomarkers, and even as putative targets for the development of novel therapeutics, not only for the eye but for many other systemic pathologies.

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硫酸肝素蛋白聚糖(HSPGs)的晶状体
硫酸乙酰肝素蛋白多糖(HSPGs)存在于大多数细胞中;在它们的表面、在细胞周围环境和/或细胞外基质中。在眼睛中,HSPG可以协调眼睛环境中发现的关键信号分子的活动,促进其发育和稳态。到目前为止,我们对单个HSPG家族成员所扮演的特定角色及其相关硫酸化HS链的异质性的理解还处于初级阶段。晶状体是一种相对简单且特征良好的眼组织,为展示和模拟单个HSPG的表达和独特作用提供了理想的舞台。单个HSPG核心蛋白以时间和空间发育和细胞类型特异性的方式不同地定位于眼组织,其缺失或功能破坏导致晶状体和其他眼组织的独特表型结果。最近的研究发现,不同的HS硫酸化酶也以细胞和组织特异性的方式存在,这些不同硫酸化模式的破坏会影响特定的HS蛋白相互作用。毫不奇怪,据报道,这些硫酸化HS链也是晶状体和眼睛发育所必需的,HS链结构和功能的失调导致发病机制和眼睛相关表型。在晶状体中,HSPG在表达和功能上发生显著而特异的变化,这可以驱动病理学,或者在某些情况下促进组织修复。作为主要的信号调节因子,HSPG有一天可能成为有价值的生物标志物,甚至可能成为开发新疗法的假定靶点,不仅对眼睛,而且对许多其他系统性疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
34.10
自引率
5.10%
发文量
78
期刊介绍: Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists. The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.
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