Ozone exposure induced kidney damage in diabetic mice: the key role of lipid metabolism and water-electrolyte homeostasis

IF 7.6 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environmental Pollution Pub Date : 2025-03-02 DOI:10.1016/j.envpol.2025.125963

Yaru Zhang, Zhipeng Yan, Nan Nan, Shiya Li, Guohua Qin

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引用次数: 0

Abstract

Ozone (O₃) is an important environmental pollutant that has garnered growing public concern. Epidemiological studies indicate that exposure to O₃ is associated with an elevated risk of kidney disease, a common complication of diabetes. However, the harmful effects of O₃ on the kidneys remain unconfirmed. Herein, we established models for non-diabetic and diabetic mice exposed to 0.5 ppm O₃ for 28 days (4 h/day). We evaluated O₃-induced renal injury and potential mechanisms through analyzing biochemical markers related to renal function, along with histopathology and transcriptomic sequencing of the kidneys. The results showed that O₃ exposure caused glomerular hypertrophy in both non-diabetic and diabetic mice, with mesangial hypercellularity and kidney function impairment specifically in diabetic mice. Furthermore, renal levels of free fatty acids and cholesterol were significantly elevated in O₃-exposed diabetic mice. The important roles of lipid and water-electrolyte metabolism related pathways in O₃-induced kidney damage were found by transcriptome sequencing analysis. The mRNA and/or protein expressions of some genes involved in β-ENaC and AQP2 pathways, which are related to renal water and sodium retention, were changed in diabetic mice following O₃ exposure by real-time quantitative PCR, immunofluorescence staining, and Western blotting. Overall, diabetic mice exhibit a higher vulnerability to adverse effects in the kidney after O₃ exposure than non-diabetic mice. Dysregulation of lipid metabolism and imbalance in water-electrolyte homeostasis have been discovered as key contributing mechanisms. This study offers valuable insights into mechanisms through which ambient O₃ poses renal health risks to both the general subjects and susceptible individuals.

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臭氧（O3）是一种重要的环境污染物，越来越受到公众的关注。流行病学研究表明，暴露于 O3 与肾脏疾病风险升高有关，而肾脏疾病是糖尿病的常见并发症。然而，臭氧对肾脏的有害影响仍未得到证实。在此，我们为非糖尿病和糖尿病小鼠建立了暴露于 0.5 ppm O3 28 天（每天 4 小时）的模型。我们通过分析与肾功能相关的生化指标以及肾脏的组织病理学和转录组测序，评估了 O3 诱导的肾损伤和潜在机制。结果表明，暴露于 O3 会导致非糖尿病小鼠和糖尿病小鼠肾小球肥大，尤其是糖尿病小鼠肾系膜细胞增生，肾功能受损。此外，暴露于 O3 的糖尿病小鼠肾脏游离脂肪酸和胆固醇水平显著升高。通过转录组测序分析发现，脂质和水电解质代谢相关通路在 O3 诱导的肾损伤中发挥着重要作用。通过实时定量 PCR、免疫荧光染色和 Western 印迹分析，发现糖尿病小鼠暴露于 O3 后，β-ENaC 和 AQP2 通路中与肾脏水钠潴留有关的一些基因的 mRNA 和/或蛋白表达发生了变化。总体而言，与非糖尿病小鼠相比，糖尿病小鼠在暴露于 O3 后更容易受到肾脏的不利影响。研究发现，脂质代谢失调和水电解质平衡失调是主要的致病机制。这项研究为了解环境中的臭氧对普通人和易感人群的肾脏健康造成危害的机制提供了宝贵的见解。

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来源期刊

Environmental Pollution 环境科学-环境科学

CiteScore

16.00

自引率

6.70%

发文量

2082

审稿时长

2.9 months

期刊介绍： Environmental Pollution is an international peer-reviewed journal that publishes high-quality research papers and review articles covering all aspects of environmental pollution and its impacts on ecosystems and human health. Subject areas include, but are not limited to: • Sources and occurrences of pollutants that are clearly defined and measured in environmental compartments, food and food-related items, and human bodies; • Interlinks between contaminant exposure and biological, ecological, and human health effects, including those of climate change; • Contaminants of emerging concerns (including but not limited to antibiotic resistant microorganisms or genes, microplastics/nanoplastics, electronic wastes, light, and noise) and/or their biological, ecological, or human health effects; • Laboratory and field studies on the remediation/mitigation of environmental pollution via new techniques and with clear links to biological, ecological, or human health effects; • Modeling of pollution processes, patterns, or trends that is of clear environmental and/or human health interest; • New techniques that measure and examine environmental occurrences, transport, behavior, and effects of pollutants within the environment or the laboratory, provided that they can be clearly used to address problems within regional or global environmental compartments.