在横纹肌溶解引起的肾损伤中,Galectin-3 可保护远端曲小管。

IF 2.9 4区 医学 Q2 PHYSIOLOGY
Vera A Kulow, Robert Labes, Claudia S Czopek, Christian Rosenberger, Michael Fähling
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引用次数: 0

摘要

高级糖化终产物(AGEs)会导致包括肾脏疾病在内的各种病症的细胞损伤。急性肾损伤(AKI)是一种很少以单一、独特的病理生理原因为特征的综合征。横纹肌溶解诱发的急性肾损伤(RIAKI)约占急性肾损伤病例的 15%,但人们对其潜在的病理生理学仍知之甚少。利用肌肉注射甘油诱导的小鼠 RIAKI 模型,我们观察到肾脏中 AGEs 和 AGE 受体 galectin-3 (LGALS3) 水平升高。免疫荧光将 LGALS3 定位于远端肾小球节段。根据新一代测序的转录组分析,RIAKI导致肾脏代谢、氧化应激和炎症发生了深刻变化。肾损伤标志物KIM-1和NGAL显示,近端和远端肾小管都存在明显的细胞压力。然而,只有近端肾小管表现出明显的损伤和凋亡,分别由常规形态学、活性 Caspase-3 和 TUNEL 试验检测到。在体外,受到 AGEs 挑战的远端曲细管(DCT)细胞会发生凋亡,而 Lgals3 siRNA 处理会显著增强凋亡。因此,在 RIAKI 中,LGALS3 的上调可能会保护远端肾小管免受 AGE 介导的损伤,而缺乏 LGALS3 的近端肾小管则处于危险之中。因此,如果能刺激近端肾小管中的 LGALS3,可能会减轻 RIAKI。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Galectin-3 protects distal convoluted tubules in rhabdomyolysis-induced kidney injury.

Galectin-3 protects distal convoluted tubules in rhabdomyolysis-induced kidney injury.

Advanced glycation endproducts (AGEs) contribute to cellular damage of various pathologies, including kidney diseases. Acute kidney injury (AKI) represents a syndrome seldom characterized by a single, distinct pathophysiological cause. Rhabdomyolysis-induced acute kidney injury (RIAKI) constitutes roughly 15% of AKI cases, yet its underlying pathophysiology remains poorly understood. Using a murine model of RIAKI induced by muscular glycerol injection, we observed elevated levels of AGEs and the AGE receptor galectin-3 (LGALS3) in the kidney. Immunofluorescence localized LGALS3 to distal nephron segments. According to transcriptomic profiling via next-generation sequencing, RIAKI led to profound changes in kidney metabolism, oxidative stress, and inflammation. Cellular stress was evident in both proximal and distal tubules, as shown by kidney injury markers KIM-1 and NGAL. However, only proximal tubules exhibited overt damage and apoptosis, as detected by routine morphology, active Caspase-3, and TUNEL assay, respectively. In vitro, distal convoluted tubule (DCT) cells challenged with AGEs underwent apoptosis, which was markedly enhanced by Lgals3 siRNA treatment. Thus, in RIAKI, the upregulation of LGALS3 may protect the distal nephron from AGE-mediated damage, while proximal tubules lacking LGALS3 stay at risk. Thus, stimulating LGALS3 in the proximal nephron, if achievable, may attenuate RIAKI.

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来源期刊
CiteScore
8.80
自引率
2.20%
发文量
121
审稿时长
4-8 weeks
期刊介绍: Pflügers Archiv European Journal of Physiology publishes those results of original research that are seen as advancing the physiological sciences, especially those providing mechanistic insights into physiological functions at the molecular and cellular level, and clearly conveying a physiological message. Submissions are encouraged that deal with the evaluation of molecular and cellular mechanisms of disease, ideally resulting in translational research. Purely descriptive papers covering applied physiology or clinical papers will be excluded. Papers on methodological topics will be considered if they contribute to the development of novel tools for further investigation of (patho)physiological mechanisms.
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