Yuxin Lin , Hao Li , Shukai Zheng , Rui Han , Kusheng Wu , Shijie Tang , Xiaoping Zhong , Jiasheng Chen
{"title":"阐明烟草烟雾诱发的颅面畸形:跨物种多组学分析揭示生物标志物和 MAPK 信号失调","authors":"Yuxin Lin , Hao Li , Shukai Zheng , Rui Han , Kusheng Wu , Shijie Tang , Xiaoping Zhong , Jiasheng Chen","doi":"10.1016/j.ecoenv.2024.117343","DOIUrl":null,"url":null,"abstract":"<div><div>Tobacco smoke (TS), particularly secondhand and thirdhand smoke, poses a pervasive and intractable environmental hazard that promotes teratogenesis and the progression of craniofacial malformations, although the underlying mechanisms remain elusive. Using zebrafish larvae as a model, our research demonstrated a correlation between the increasing concentration of cigarette smoke extract (CSE) and the severity of craniofacial malformations, supported by Alcian blue staining and histological assessments. Through a combined mRNA-miRNA analysis and quantitative real-time PCR, we identified <em>miR-96–5p</em>, <em>miR-152</em>, <em>miR-125b-2–3p</em>, and <em>miR-181a-3–3p</em> as pivotal biomarkers in craniofacial cartilage development. Functional analyses revealed their association with the MAPK signaling pathway, oxidative stress (OS), and cell development, highlighting MAPK as a crucial mediator. Single-cell transcriptomics further disclosed aberrant MAPK activation in mesenchymal cells. Subsequent investigations in human embryonic palatal mesenchymal (HEPM) cells confirmed similar patterns of growth inhibition, apoptosis, and OS, and emphasized the cross-species consistency of these biomarkers and the over-activation of the MAPK signaling pathway. A comprehensive tri-omics analysis of HEPM cells identified pivotal genes, proteins, and metabolites within the MAPK pathway. This groundbreaking cross-species multi-omics study unveils novel biomarkers and MAPK pathway perturbations linked to TS-induced craniofacial developmental toxicity, promoting innovative clinical prediction, diagnosis, and interventional strategies to tackle TS-induced craniofacial malformations.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"288 ","pages":"Article 117343"},"PeriodicalIF":6.2000,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Elucidating tobacco smoke-induced craniofacial deformities: Biomarker and MAPK signaling dysregulation unraveled by cross-species multi-omics analysis\",\"authors\":\"Yuxin Lin , Hao Li , Shukai Zheng , Rui Han , Kusheng Wu , Shijie Tang , Xiaoping Zhong , Jiasheng Chen\",\"doi\":\"10.1016/j.ecoenv.2024.117343\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Tobacco smoke (TS), particularly secondhand and thirdhand smoke, poses a pervasive and intractable environmental hazard that promotes teratogenesis and the progression of craniofacial malformations, although the underlying mechanisms remain elusive. Using zebrafish larvae as a model, our research demonstrated a correlation between the increasing concentration of cigarette smoke extract (CSE) and the severity of craniofacial malformations, supported by Alcian blue staining and histological assessments. Through a combined mRNA-miRNA analysis and quantitative real-time PCR, we identified <em>miR-96–5p</em>, <em>miR-152</em>, <em>miR-125b-2–3p</em>, and <em>miR-181a-3–3p</em> as pivotal biomarkers in craniofacial cartilage development. Functional analyses revealed their association with the MAPK signaling pathway, oxidative stress (OS), and cell development, highlighting MAPK as a crucial mediator. Single-cell transcriptomics further disclosed aberrant MAPK activation in mesenchymal cells. Subsequent investigations in human embryonic palatal mesenchymal (HEPM) cells confirmed similar patterns of growth inhibition, apoptosis, and OS, and emphasized the cross-species consistency of these biomarkers and the over-activation of the MAPK signaling pathway. A comprehensive tri-omics analysis of HEPM cells identified pivotal genes, proteins, and metabolites within the MAPK pathway. This groundbreaking cross-species multi-omics study unveils novel biomarkers and MAPK pathway perturbations linked to TS-induced craniofacial developmental toxicity, promoting innovative clinical prediction, diagnosis, and interventional strategies to tackle TS-induced craniofacial malformations.</div></div>\",\"PeriodicalId\":303,\"journal\":{\"name\":\"Ecotoxicology and Environmental Safety\",\"volume\":\"288 \",\"pages\":\"Article 117343\"},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-11-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ecotoxicology and Environmental Safety\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0147651324014192\",\"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":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0147651324014192","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}
Elucidating tobacco smoke-induced craniofacial deformities: Biomarker and MAPK signaling dysregulation unraveled by cross-species multi-omics analysis
Tobacco smoke (TS), particularly secondhand and thirdhand smoke, poses a pervasive and intractable environmental hazard that promotes teratogenesis and the progression of craniofacial malformations, although the underlying mechanisms remain elusive. Using zebrafish larvae as a model, our research demonstrated a correlation between the increasing concentration of cigarette smoke extract (CSE) and the severity of craniofacial malformations, supported by Alcian blue staining and histological assessments. Through a combined mRNA-miRNA analysis and quantitative real-time PCR, we identified miR-96–5p, miR-152, miR-125b-2–3p, and miR-181a-3–3p as pivotal biomarkers in craniofacial cartilage development. Functional analyses revealed their association with the MAPK signaling pathway, oxidative stress (OS), and cell development, highlighting MAPK as a crucial mediator. Single-cell transcriptomics further disclosed aberrant MAPK activation in mesenchymal cells. Subsequent investigations in human embryonic palatal mesenchymal (HEPM) cells confirmed similar patterns of growth inhibition, apoptosis, and OS, and emphasized the cross-species consistency of these biomarkers and the over-activation of the MAPK signaling pathway. A comprehensive tri-omics analysis of HEPM cells identified pivotal genes, proteins, and metabolites within the MAPK pathway. This groundbreaking cross-species multi-omics study unveils novel biomarkers and MAPK pathway perturbations linked to TS-induced craniofacial developmental toxicity, promoting innovative clinical prediction, diagnosis, and interventional strategies to tackle TS-induced craniofacial malformations.
期刊介绍:
Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.