Air pollution aggravates renal ischaemia–reperfusion-induced acute kidney injury

IF 5.6 2区医学 Q1 ONCOLOGY

The Journal of Pathology Pub Date : 2024-06-27 DOI:10.1002/path.6302

Talita Rojas Sanches, Antonio Carlos Parra, Peiqi Sun, Mariana Pereira Graner, Lucas Yuji Umesaki Itto, Loes Maria Butter, Nike Claessen, Joris JTH Roelofs, Sandrine Florquin, Mariana Matera Veras, Maria de Fatima Andrade, Paulo Hilário Nascimento Saldiva, Jesper Kers, Lucia Andrade, Alessandra Tammaro

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引用次数: 0

Abstract

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM_2.5) and a decline in renal function. PM_2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia–reperfusion injury (IRI) involves biological processes similar to those involved in PM_2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM_2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM_2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM_2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM_2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP–AMP synthase-stimulator of interferon genes (cGAS–STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM_2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM_2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM_2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM_2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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空气污染会加重肾缺血再灌注引起的急性肾损伤。

慢性肾脏病（CKD）已成为全球公共卫生的重大问题。最近的流行病学研究强调了暴露于细颗粒物（PM2.5）与肾功能下降之间的联系。PM2.5 通过氧化应激和炎症对各种器官产生有害影响。缺血再灌注损伤（IRI）导致的急性肾损伤（AKI）涉及的生物过程与PM2.5毒性所涉及的生物过程相似，是导致慢性肾功能衰竭的已知风险因素。本研究旨在探讨 PM2.5 暴露对 IRI 诱导的 AKI 的影响。通过独特的环境控制装置，小鼠在IRI前暴露于城市PM2.5或过滤空气12周，然后在手术后48小时安乐死。暴露于PM2.5和IRI的动物表现出肾小球滤过功能降低、尿液浓缩能力受损和肾小管明显损伤。此外，PM2.5还加剧了局部先天性免疫反应和线粒体功能障碍，并增强了环GMP-AMP合成酶-干扰素基因刺激器（cGAS-STING）通路的激活。这增加了肾脏衰老，抑制了抗衰老蛋白 klotho，导致早期纤维化变化。利用暴露于PM2.5和缺氧/复氧的近端肾小管上皮细胞进行的体外研究显示，由细胞质线粒体DNA引发的STING通路活化增强，导致肾小管损伤加重和促炎表型。总之，我们的研究结果表明，PM2.5 可使近端肾小管上皮细胞对 IRI 诱导的损伤敏感，这表明 PM2.5 暴露与发生 AKI 的个体对 CKD 的易感性增加之间存在着合理的联系。旨在降低PM2.5浓度和实施预防措施的策略可改善AKI患者的预后，并缓解从AKI到CKD的进展。© 2024 作者。病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。

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

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.