Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Québec City, QC G1V 0A6, Canada.
Centre de Recherche du CHU de Québec, Axe Médecine Régénératrice, Québec City, QC G1J 1Z4, Canada.
Int J Mol Sci. 2023 Aug 24;24(17):13182. doi: 10.3390/ijms241713182.
Clusterin (CLU) is a glycoprotein originally discovered in 1983 in ram testis fluid. Rapidly observed in other tissues, it was initially given various names based on its function in different tissues. In 1992, it was finally named CLU by consensus. Nearly omnipresent in human tissues, CLU is strongly expressed at fluid-tissue interfaces, including in the eye and in particular the cornea. Recent research has identified different forms of CLU, with the most prominent being a 75-80 kDa heterodimeric protein that is secreted. Another truncated version of CLU (55 kDa) is localized to the nucleus and exerts pro-apoptotic activities. CLU has been reported to be involved in various physiological processes such as sperm maturation, lipid transportation, complement inhibition and chaperone activity. CLU was also reported to exert important functions in tissue remodeling, cell-cell adhesion, cell-substratum interaction, cytoprotection, apoptotic cell death, cell proliferation and migration. Hence, this protein is sparking interest in tissue wound healing. Moreover, gene expression is finely regulated by cytokines, growth factors and stress-inducing agents, leading to abnormally elevated levels of CLU in many states of cellular disturbance, including cancer and neurodegenerative conditions. In the eye, CLU expression has been reported as being severely increased in several pathologies, such as age-related macular degeneration and Fuch's corneal dystrophy, while it is depleted in others, such as pathologic keratinization. Nevertheless, the precise role of CLU in the development of ocular pathologies has yet to be deciphered. The question of whether CLU expression is influenced by these disorders or contributes to them remains open. In this article, we review the actual knowledge about CLU at both the protein and gene expression level in wound healing, and explore the possibility that CLU is a key factor in cancer and eye diseases. Understanding the expression and regulation of CLU could lead to the development of novel therapeutics for promoting wound healing.
簇集蛋白 (CLU) 是一种糖蛋白，于 1983 年在公羊睾丸液中首次发现。在其他组织中迅速被观察到后，最初根据其在不同组织中的功能赋予了各种名称。1992 年，最终通过共识将其命名为 CLU。CLU 几乎存在于人体组织中，在包括眼睛在内的组织-液界面强烈表达，特别是在角膜中。最近的研究已经确定了 CLU 的不同形式，其中最突出的是一种 75-80 kDa 的异二聚体分泌蛋白。CLU 的另一种截断形式（55 kDa）定位于细胞核并发挥促凋亡作用。CLU 被报道参与各种生理过程，如精子成熟、脂质运输、补体抑制和伴侣活性。CLU 还被报道在组织重塑、细胞-细胞黏附、细胞-基质相互作用、细胞保护、细胞凋亡、细胞增殖和迁移中发挥重要作用。因此，这种蛋白在组织伤口愈合中引起了人们的兴趣。此外，基因表达受细胞因子、生长因子和应激诱导剂的精细调控，导致 CLU 在许多细胞紊乱状态下的异常高水平，包括癌症和神经退行性疾病。在眼睛中，CLU 表达在几种病理学中被报道严重增加，如年龄相关性黄斑变性和 Fuch 角膜营养不良，而在其他疾病中如病理性角化中则耗尽。然而，CLU 在眼部病变发展中的确切作用尚未被破译。CLU 表达是否受这些疾病影响或导致这些疾病仍未可知。在本文中，我们综述了在伤口愈合中 CLU 在蛋白质和基因表达水平上的实际知识，并探讨了 CLU 是否是癌症和眼部疾病的关键因素。了解 CLU 的表达和调控可能会导致开发促进伤口愈合的新型治疗方法。
