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眼表面黏蛋白型 O-聚糖的结构和生物学作用。

Structure and biological roles of mucin-type O-glycans at the ocular surface.

机构信息

Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.

出版信息

Ocul Surf. 2010 Jan;8(1):8-17. doi: 10.1016/s1542-0124(12)70213-6.

Abstract

Mucins are major components in mucus secretions and apical cell membranes on wet-surfaced epithelia. Structurally, they are characterized by the presence of tandem repeat domains containing heavily O-glycosylated serine and threonine residues. O-glycans contribute to maintaining the highly extended and rigid structure of mucins, conferring to them specific physical and biological properties essential for their protective functions. at the ocular surface epithelia, mucin-type O-glycan chains are short and predominantly sialylated, perhaps reflecting specific requirements of the ocular surface. Traditionally, secreted mucins and their O-glycans in the tear film have been involved in the clearance of debris and pathogens from the surface of the eye. New evidence, however, shows that O-glycans on the cell-surface glycocalyx have additional biological roles in the protection of corneal and conjunctival epithelia, such as preventing bacterial adhesion, promoting boundary lubrication, and maintaining the epithelial barrier function through their interaction with galectin-3. Abnormalities in mucin-type O-glycosylation have been identified in many disorders where the stability of the ocular surface is compromised. This review summarizes recent advances in understanding the structure, biosynthesis, and function of mucin-type O-glycans at the ocular surface and their alteration in ocular surface disease.

摘要

黏蛋白是湿润表面上皮细胞的黏液分泌物和顶膜的主要成分。从结构上看,它们的特征是存在串联重复结构域,其中包含高度 O-糖基化的丝氨酸和苏氨酸残基。O-聚糖有助于维持黏蛋白的高度伸展和刚性结构,赋予它们特定的物理和生物学特性,这对它们的保护功能至关重要。在眼表面上皮中,黏蛋白型 O-聚糖链较短且主要是唾液酸化的,这可能反映了眼表面的特殊需求。传统上,泪膜中的分泌型黏蛋白及其 O-聚糖参与清除眼表面的碎屑和病原体。然而,新的证据表明,细胞表面糖萼上的 O-聚糖在保护角膜和结膜上皮方面具有额外的生物学作用,例如防止细菌黏附、促进边界润滑以及通过与半乳糖凝集素-3 的相互作用维持上皮屏障功能。在眼表面稳定性受到损害的许多疾病中,已经确定了黏蛋白型 O-糖基化的异常。本综述总结了近年来在理解眼表面黏蛋白型 O-聚糖的结构、生物合成和功能及其在眼表面疾病中的改变方面的进展。

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