Contrast-Induced Acute Kidney Injury is Modulated by Circadian CLOCK/NRF2 Pathway

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
IUBMB Life Pub Date : 2025-05-20 DOI:10.1002/iub.70022
Shuqing Yang, Xinxin Xu, Lulu Wang, Yi Fang, Yang Zhou, Chunsun Dai, Lei Jiang, Boqing Zhang, Jing Luo
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Abstract

Numerous kidney functions exhibit substantial circadian oscillations, such as renal blood flow, glomerular filtration rate, tubular reabsorption function, and erythropoietin production. The onset and the injury of acute kidney injury caused by ischemia or drugs also have a circadian rhythmicity. Contrast media are widely used in clinical diagnosis and treatment; however, whether contrast-induced kidney injury exhibits a time-of-day dependence is unknown. We retrospectively analyzed 33 patients who underwent percutaneous coronary angiography and found that contrast induced the increase of serum neutrophil gelatinase-associated lipocalin (NGAL) was more obvious in the group who underwent operation during 6:00 ~ 13:00 than the group who underwent operation between 13:00 ~ 20:00. In addition, C57BL/6J mice were injected with iohexol at different times. The kidney injury of mice injected with iohexol at ZT12 was more severe than that at ZT0, which was manifested in the increase of urinary KIM1 and NGAL, enhanced renal tubular lipid peroxidation, and increased tubular ferroptosis. Inhibition of ferroptosis could alleviate kidney injury induced by iohexol at ZT12. Mechanistically, we found that nuclear factor erythrocyte 2-associated factor 2 (NRF2) expression has a 24-h circadian rhythm and is directly regulated by CLOCK. Administration of 4-Octyl itaconate at ZT12 to increase NRF2 expression could attenuate iohexol-induced tubular ferroptosis. These findings provide a new insight into the pathology of contrast medium-induced kidney injury, in which oscillatory NRF2 expression regulated by CLOCK contributes to the susceptibility of contrast-induced kidney injury in a time-of-day–specific fashion.

对比剂诱导的急性肾损伤受昼夜节律时钟/NRF2通路调控
许多肾脏功能表现出明显的昼夜振荡,如肾血流量、肾小球滤过率、肾小管重吸收功能和促红细胞生成素的产生。缺血或药物引起的急性肾损伤的发生和损伤也具有昼夜节律性。造影剂广泛应用于临床诊断和治疗;然而,对比剂引起的肾损伤是否表现出时间依赖性尚不清楚。我们回顾性分析33例经皮冠状动脉造影患者,发现造影剂引起的血清中性粒细胞明胶酶相关脂钙蛋白(NGAL)升高在6:00 ~ 13:00手术组比在13:00 ~ 20:00手术组更为明显。另外,在不同时间给C57BL/6J小鼠注射碘己醇。在ZT12时注射碘己醇小鼠的肾损伤较ZT0时更为严重,表现为尿中KIM1和NGAL升高,肾小管脂质过氧化增强,肾小管铁吊增高。抑制铁下垂可减轻碘己醇所致ZT12肾损伤。在机制上,我们发现核因子红细胞2相关因子2 (NRF2)的表达具有24小时昼夜节律,并直接受CLOCK调节。在ZT12时给予衣康酸4-辛酯以增加NRF2表达,可减轻碘己醇诱导的管状铁下垂。这些发现为造影剂诱导的肾损伤病理学提供了新的见解,其中由CLOCK调节的振荡NRF2表达以一天中特定时间的方式促进造影剂诱导的肾损伤的易感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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