Multi-Omics Analyses Reveal the Mechanisms of Early Stage Kidney Toxicity by Diquat

被引:8
|
作者
Zhang, Huazhong [1 ,2 ]
Zhang, Jinsong [1 ,2 ]
Li, Jinquan [1 ,2 ]
Mao, Zhengsheng [2 ]
Qian, Jian [3 ]
Zong, Cheng [4 ]
Sun, Hao [1 ,2 ]
Yuan, Beilei [4 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Emergency, Nanjing 210029, Peoples R China
[2] Nanjing Med Univ, Inst Poisoning, Nanjing 211100, Peoples R China
[3] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
[4] Nanjing Tech Univ, Coll Safety Sci & Engn, Nanjing 211816, Peoples R China
基金
中国国家自然科学基金;
关键词
diquat; kidney injury; multi-omics; fatty acid metabolism; PPAR signaling pathway;
D O I
10.3390/toxics11020184
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Diquat (DQ), a widely used bipyridyl herbicide, is associated with significantly higher rates of kidney injuries compared to other pesticides. However, the underlying molecular mechanisms are largely unknown. In this study, we identified the molecular changes in the early stage of DQ-induced kidney damage in a mouse model through transcriptomic, proteomic and metabolomic analyses. We identified 869 genes, 351 proteins and 96 metabolites that were differentially expressed in the DQ-treated mice relative to the control mice (p < 0.05), and showed significant enrichment in the PPAR signaling pathway and fatty acid metabolism. Hmgcs2, Cyp4a10, Cyp4a14 and Lpl were identified as the major proteins/genes associated with DQ-induced kidney damage. In addition, eicosapentaenoic acid, linoleic acid, palmitic acid and (R)-3-hydroxybutyric acid were the major metabolites related to DQ-induced kidney injury. Overall, the multi-omics analysis showed that DQ-induced kidney damage is associated with dysregulation of the PPAR signaling pathway, and an aberrant increase in Hmgcs2 expression and 3-hydroxybutyric acid levels. Our findings provide new insights into the molecular basis of DQ-induced early kidney damage.
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页数:12
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