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自噬在肾脏疾病中的作用:研究进展与治疗潜力。

Autophagy in kidney disease: Advances and therapeutic potential.

机构信息

Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York, NY, United States.

Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York, NY, United States.

出版信息

Prog Mol Biol Transl Sci. 2020;172:107-133. doi: 10.1016/bs.pmbts.2020.01.008. Epub 2020 Feb 3.

DOI:10.1016/bs.pmbts.2020.01.008
PMID:32620239
Abstract

Autophagy is a highly conserved intracellular catabolic process for the degradation of cytoplasmic components that has recently gained increasing attention for its importance in kidney diseases. It is indispensable for the maintenance of kidney homeostasis both in physiological and pathological conditions. Investigations utilizing various kidney cell-specific conditional autophagy-related gene knockouts have facilitated the advancement in understanding of the role of autophagy in the kidney. Recent findings are raising the possibility that defective autophagy exerts a critical role in different pathological conditions of the kidney. An emerging body of evidence reveals that autophagy exhibits cytoprotective functions in both glomerular and tubular compartments of the kidney, suggesting the upregulation of autophagy as an attractive therapeutic strategy. However, there is also accumulating evidence that autophagy could be deleterious, which presents a formidable challenge in developing therapeutic strategies targeting autophagy. Here, we review the recent advances in research on the role of autophagy during different pathological conditions, including acute kidney injury (AKI), focusing on sepsis, ischemia-reperfusion injury, cisplatin, and heavy metal-induced AKI. We also discuss the role of autophagy in chronic kidney disease (CKD) focusing on the pathogenesis of tubulointerstitial fibrosis, podocytopathies including focal segmental glomerulosclerosis, diabetic nephropathy, IgA nephropathy, membranous nephropathy, HIV-associated nephropathy, and polycystic kidney disease.

摘要

自噬是一种高度保守的细胞内降解细胞质成分的分解代谢过程,最近因其在肾脏疾病中的重要性而受到越来越多的关注。它对于维持生理和病理条件下的肾脏内环境稳定是不可或缺的。利用各种肾脏细胞特异性条件性自噬相关基因敲除的研究促进了对自噬在肾脏中的作用的理解。最近的发现提出了一种可能性,即自噬缺陷在肾脏的不同病理条件下发挥关键作用。越来越多的证据表明,自噬在肾脏的肾小球和肾小管部分均具有细胞保护功能,提示上调自噬作为一种有吸引力的治疗策略。然而,也有越来越多的证据表明自噬可能是有害的,这在开发针对自噬的治疗策略方面带来了巨大的挑战。在这里,我们综述了自噬在不同病理条件下作用的研究进展,包括急性肾损伤 (AKI),重点关注脓毒症、缺血再灌注损伤、顺铂和重金属诱导的 AKI。我们还讨论了自噬在慢性肾脏病 (CKD) 中的作用,重点讨论了肾小管间质纤维化的发病机制、足细胞病,包括局灶节段性肾小球硬化症、糖尿病肾病、IgA 肾病、膜性肾病、HIV 相关肾病和多囊肾病。

相似文献

1
Autophagy in kidney disease: Advances and therapeutic potential.自噬在肾脏疾病中的作用:研究进展与治疗潜力。
Prog Mol Biol Transl Sci. 2020;172:107-133. doi: 10.1016/bs.pmbts.2020.01.008. Epub 2020 Feb 3.
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Autophagy in renal diseases.肾脏疾病中的自噬
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Implications of autophagy for glomerular aging and disease.自噬对肾小球衰老和疾病的影响。
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Autophagy in kidney homeostasis and disease.自噬在肾脏稳态和疾病中的作用。
Nat Rev Nephrol. 2020 Sep;16(9):489-508. doi: 10.1038/s41581-020-0309-2. Epub 2020 Jul 23.
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Autophagy: emerging therapeutic target for diabetic nephropathy.自噬:糖尿病肾病新出现的治疗靶点
Semin Nephrol. 2014 Jan;34(1):9-16. doi: 10.1016/j.semnephrol.2013.11.003. Epub 2013 Nov 21.
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Autophagy in glomerular health and disease.肾小球健康与疾病中的自噬
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Targeting podocyte-associated diseases.靶向足细胞相关疾病。
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Autophagy in diabetic nephropathy.糖尿病肾病中的自噬
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Autophagy in acute kidney injury.急性肾损伤中的自噬
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Rictor/mTORC2 protects against cisplatin-induced tubular cell death and acute kidney injury.雷帕霉素靶蛋白复合体 2(Rictor/mTORC2)可防止顺铂诱导的肾小管细胞死亡和急性肾损伤。
Kidney Int. 2014 Jul;86(1):86-102. doi: 10.1038/ki.2013.559. Epub 2014 Jan 22.

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