铜稳态失衡与肾脏纤维化的研究进展

Research progress on association of copper homeostasis dysregulation with kidney fibrosis

关键词:  铜  铜伴侣蛋白  赖氨酸氧化酶  肾脏纤维化

Key words:  copper  copper chaperones  lysyl oxidase  renal fibrosis

摘要:

肾脏纤维化是各种慢性肾脏病进展至终末期肾病的共同病理表现及病理生理基础。其主要特征包括细胞外基质的异常合成和堆积，伴随着炎性细胞渗透、肾小管萎缩以及周围毛细血管网络的减少等病理改变。这些变化导致肾实质逐渐减少，最终引发肾功能衰竭。肾脏纤维化的机制复杂，目前缺乏特异性治疗靶点，难以延缓或阻止其进展。铜离子是人体中不可或缺的微量元素，作为多种蛋白和酶的催化结构或辅助因子，参与多个生物学过程，如能量生成、皮肤色素生成、自由基清除和细胞增殖等。既往研究已证实铜离子与肝脏纤维化和肺纤维化相关，近期研究发现铜离子也可能参与肾脏纤维化的发生。本文将从铜离子在机体和细胞代谢中的角色入手，总结铜及相关蛋白在肾脏纤维化中的作用机制，为深入探讨肾脏纤维化的发生和发展提供新的研究视角。

Abstract:

Renal fibrosis is a common outcome of chronic kidney diseases progressing to the end stage. It characterized by abnormal synthesis and deposit of extracellular matrix, and its pathological changes, like inflammatory cell infiltration, tubular atrophy, and reduced capillary network, contribute to a gradual decline of renal parenchyma, resulting in functional failure. The complex mechanisms of renal fibrosis lack specific treatment targets for effective intervention. Copper ions, essential trace elements, act as catalysts or auxiliary factors in various biological processes，including energy generation, melanin synthesis, free radical clearance, and cell proliferation. It has been revealed that copper ions are involved in liver or pulmonary fibrosis, and recent studies propose a potential role of copper ions in renal fibrosis. This article reviews the roles and mechanisms of copper ions and related proteins in the occurrence and development of renal fibrosis from the perspective of body and cell metabolism, to provide insights for further research on the relationship between copper homeostasis dysregulation and kidney fibrosis.