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肾脏再生的细胞修复方法与手段。

Ways and Means of Cellular Reconditioning for Kidney Regeneration.

作者信息

Ishiko Shinya, Goligorsky Michael S

机构信息

Department of Medicine, New York Medical College, Valhalla, New York, USA,

Department of Medicine, Physiology and Pharmacology, New York Medical College, Valhalla, New York, USA.

出版信息

Am J Nephrol. 2022;53(2-3):96-107. doi: 10.1159/000522050. Epub 2022 Mar 8.

Abstract

BACKGROUND

Mitochondrial, lysosomal, and peroxisomal dysfunction; defective autophagy; mitophagy; and pexophagy, as well as the loss of glycocalyx integrity are known contributors to initiation and progression of diverse kidney diseases. Those cellular organelles are tightly interactive in health, and during development of a disease, damage in one may propagate to others. By extension, it follows that restoring an individual defect may culminate in a broader restorative spectrum and improvement of cell and organ functions.

SUMMARY

A novel strategy of reconditioning cellular organellar dysfunction, which we define as refurbishment of pathogenically pivotal intra- or extracellular elements, damaged in the course of disease and impeding restoration, is briefly outlined in this overview. Individual therapeutic reconditioning approaches targeting selected organelles are cataloged. We anticipate that the proposed reconditioning strategy in the future may enrich the arsenal of regenerative medicine and nephrology.

KEY MESSAGE

The arsenal of regenerative medicine and nephrology consisting of organ transplantation, use of stem cells, cell-free approaches, cell reprogramming strategies, and organ engineering has been enriched by the reconditioning strategy. The latter is based on the recognition of two facts that (a) impairment of diverse cellular organelles contributes to pathogenesis of kidney disease and (b) individual organelles are functionally interactively coupled, which explains the "domino effect" leading to their dysfunction. Reconditioning takes advantage of these facts and, while initially directed to restore the function of individual cellular organelles, culminates in the propagation of a therapeutic intervention to account for improved cell and organ function. Examples of such interventions are briefly summarized along the presentation of defective cellular organelles contributing to pathogenesis of kidney disease.

摘要

背景

线粒体、溶酶体和过氧化物酶体功能障碍;自噬缺陷;线粒体自噬;以及过氧化物酶体自噬,还有糖萼完整性的丧失,都是不同肾脏疾病发生和发展的已知因素。这些细胞器在健康状态下紧密相互作用,在疾病发展过程中,一个细胞器的损伤可能会蔓延到其他细胞器。由此推断,修复单个缺陷可能最终导致更广泛的修复范围,并改善细胞和器官功能。

总结

本综述简要概述了一种修复细胞细胞器功能障碍的新策略,我们将其定义为修复在疾病过程中受损并阻碍恢复的致病关键细胞内或细胞外元件。列出了针对选定细胞器的个别治疗性修复方法。我们预计,未来提出的修复策略可能会丰富再生医学和肾脏病学的手段。

关键信息

再生医学和肾脏病学的手段包括器官移植、干细胞的使用、无细胞方法、细胞重编程策略和器官工程,而修复策略丰富了这些手段。后者基于对两个事实的认识:(a)多种细胞器的损伤导致肾脏疾病的发病机制;(b)单个细胞器在功能上相互耦合,这解释了导致其功能障碍的“多米诺效应”。修复策略利用了这些事实,虽然最初旨在恢复单个细胞器的功能,但最终会导致治疗干预的扩展,以改善细胞和器官功能。在介绍导致肾脏疾病发病机制的有缺陷的细胞器时,简要总结了此类干预的例子。

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