Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury.

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chien-Lin Lu, Yi-Yun Wang, Yih-Jeng Tsai, Hsuan-Ting Chen, Ming-Chieh Ma, Wen-Bin Wu
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Abstract

Metabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a rat model of MetS using a high-fat diet combined with a single-dose streptozotocin injection in male Wistar rats. MetS rats exhibited systemic OxS, evidenced by elevated circulating levels of free oxygen radicals and decreased antioxidant defense capacity, as well as hypertension, renal lipid peroxidation, glomerular hyperfiltration, and renal tubular injury. Transcriptomic profiling of renal tissue revealed significant downregulation of six OxS-related genes: C-C motif chemokine ligand 5 (CCL5), glutamate-cysteine ligase catalytic subunit, glutathione peroxidase 6, recombination activating gene 2, NAD(P)H: quinone oxidoreductase 1, and selenoprotein P-1. Among these downregulated genes, CCL5 was further confirmed to be repressed at both mRNA and protein levels across intrarenal and systemic compartments. Given its documented functions in immune signaling and redox homeostasis, CCL5 downregulation may contribute to enhanced oxidative damage in MetS-associated renal injury. These findings highlight the role of redox gene dysregulation in the pathogenesis of MetS-related kidney disease and support the potential of CCL5 as a biomarker for oxidative renal injury.

代谢综合征相关肾损伤大鼠模型的转录组氧化还原失调。
代谢综合征(MetS)以肥胖、胰岛素抵抗和血脂异常为特征,是肾损伤的主要危险因素。氧化应激(OxS)在其发展过程中起关键作用;然而,潜在的分子机制尚不完全清楚。在本研究中,我们在雄性Wistar大鼠中建立了高脂肪饮食联合单剂量链脲佐菌素注射的大鼠MetS模型。MetS大鼠表现出系统性OxS,表现为循环中自由基水平升高,抗氧化防御能力下降,以及高血压、肾脂质过氧化、肾小球高滤过和肾小管损伤。肾组织转录组学分析显示6个oxs相关基因显著下调:C-C基趋化因子配体5 (CCL5)、谷氨酸-半胱氨酸连接酶催化亚基、谷胱甘肽过氧化物酶6、重组激活基因2、NAD(P)H:醌氧化还原酶1和硒蛋白P-1。在这些下调的基因中,CCL5被进一步证实在肾内和全身隔室的mRNA和蛋白水平上都受到抑制。考虑到CCL5在免疫信号传导和氧化还原稳态中的作用,CCL5下调可能有助于mets相关肾损伤中氧化损伤的增强。这些发现强调了氧化还原基因失调在met相关肾脏疾病发病机制中的作用,并支持CCL5作为氧化性肾损伤生物标志物的潜力。
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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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