Xing-Yi Wei , Pan-Pan Jia , Huan Hu , Li Liu , Tian-Yun Li , Yong-Zhi Li , De-Sheng Pei
{"title":"多组学揭示了病因不明的慢性肾脏疾病(CKDu)发病机制。","authors":"Xing-Yi Wei , Pan-Pan Jia , Huan Hu , Li Liu , Tian-Yun Li , Yong-Zhi Li , De-Sheng Pei","doi":"10.1016/j.envpol.2023.122524","DOIUrl":null,"url":null,"abstract":"<div><p><span>Chronic kidney disease of unknown etiology (CKDu) is an endemic disease in the dry zone of farming communities, Sri Lanka. The drinking water in a CKDu prevalent area contains a high concentration of F</span><sup>−</sup><span>, hardness and other environmental pollutants, including heavy metals and microcystin, which are considered possible etiology of CKDu in these areas. Here, multi-omics data with host transcriptome, metabolome and gut microbiomes were obtained using simulated local drinking water of Sri Lanka after their exposure to adult zebrafish. Based on an integrated multi-omics analysis in the context of host physiology in the kidney injury samples with different pathologic grades, two common pathways necroptosis and purine metabolism were identified as potentially important pathways that affect kidney injury. The key metabolite acetyl adenylate in the purine metabolism pathway was significantly positively correlated with </span><em>Comamonas</em> (<em>rho</em> = 0.72) and significantly negatively correlated with <em>Plesiomonas</em> (<em>rho</em><span> = −0.58). This crucial metabolite and two key gut bacteria genera may not only be potential markers but also potential therapeutic targets in the uric acid metabolic pathway, which is an important factor in the pathogenesis of acute kidney injury (AKI) in general, as well as of chronic kidney disease (CKD). Based on this, we revealed the urea metabolism pathway of kidney injury in zebrafish and provided a new avenue for the treatment of CKDu in Sri Lanka.</span></p></div>","PeriodicalId":311,"journal":{"name":"Environmental Pollution","volume":null,"pages":null},"PeriodicalIF":7.6000,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multi-omics reveal mechanisms underlying chronic kidney disease of unknown etiology (CKDu) pathogenesis using zebrafish\",\"authors\":\"Xing-Yi Wei , Pan-Pan Jia , Huan Hu , Li Liu , Tian-Yun Li , Yong-Zhi Li , De-Sheng Pei\",\"doi\":\"10.1016/j.envpol.2023.122524\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Chronic kidney disease of unknown etiology (CKDu) is an endemic disease in the dry zone of farming communities, Sri Lanka. The drinking water in a CKDu prevalent area contains a high concentration of F</span><sup>−</sup><span>, hardness and other environmental pollutants, including heavy metals and microcystin, which are considered possible etiology of CKDu in these areas. Here, multi-omics data with host transcriptome, metabolome and gut microbiomes were obtained using simulated local drinking water of Sri Lanka after their exposure to adult zebrafish. Based on an integrated multi-omics analysis in the context of host physiology in the kidney injury samples with different pathologic grades, two common pathways necroptosis and purine metabolism were identified as potentially important pathways that affect kidney injury. The key metabolite acetyl adenylate in the purine metabolism pathway was significantly positively correlated with </span><em>Comamonas</em> (<em>rho</em> = 0.72) and significantly negatively correlated with <em>Plesiomonas</em> (<em>rho</em><span> = −0.58). This crucial metabolite and two key gut bacteria genera may not only be potential markers but also potential therapeutic targets in the uric acid metabolic pathway, which is an important factor in the pathogenesis of acute kidney injury (AKI) in general, as well as of chronic kidney disease (CKD). Based on this, we revealed the urea metabolism pathway of kidney injury in zebrafish and provided a new avenue for the treatment of CKDu in Sri Lanka.</span></p></div>\",\"PeriodicalId\":311,\"journal\":{\"name\":\"Environmental Pollution\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2023-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Environmental Pollution\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0269749123015269\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Pollution","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0269749123015269","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Multi-omics reveal mechanisms underlying chronic kidney disease of unknown etiology (CKDu) pathogenesis using zebrafish
Chronic kidney disease of unknown etiology (CKDu) is an endemic disease in the dry zone of farming communities, Sri Lanka. The drinking water in a CKDu prevalent area contains a high concentration of F−, hardness and other environmental pollutants, including heavy metals and microcystin, which are considered possible etiology of CKDu in these areas. Here, multi-omics data with host transcriptome, metabolome and gut microbiomes were obtained using simulated local drinking water of Sri Lanka after their exposure to adult zebrafish. Based on an integrated multi-omics analysis in the context of host physiology in the kidney injury samples with different pathologic grades, two common pathways necroptosis and purine metabolism were identified as potentially important pathways that affect kidney injury. The key metabolite acetyl adenylate in the purine metabolism pathway was significantly positively correlated with Comamonas (rho = 0.72) and significantly negatively correlated with Plesiomonas (rho = −0.58). This crucial metabolite and two key gut bacteria genera may not only be potential markers but also potential therapeutic targets in the uric acid metabolic pathway, which is an important factor in the pathogenesis of acute kidney injury (AKI) in general, as well as of chronic kidney disease (CKD). Based on this, we revealed the urea metabolism pathway of kidney injury in zebrafish and provided a new avenue for the treatment of CKDu in Sri Lanka.
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.