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

IF 6.2 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Yuxin Lin , Hao Li , Shukai Zheng , Rui Han , Kusheng Wu , Shijie Tang , Xiaoping Zhong , Jiasheng Chen
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引用次数: 0

摘要

烟草烟雾(TS),尤其是二手烟和三手烟,是一种普遍存在且难以解决的环境危害,会促进畸胎的形成和颅面畸形的发展,但其潜在机制仍然难以捉摸。我们的研究以斑马鱼幼体为模型,通过阿尔新蓝染色和组织学评估,证明了香烟烟雾提取物(CSE)浓度的增加与颅面畸形严重程度之间的相关性。通过mRNA-miRNA联合分析和定量实时PCR,我们发现miR-96-5p、miR-152、miR-125b-2-3p和miR-181a-3-3p是颅面软骨发育过程中的关键生物标志物。功能分析揭示了它们与 MAPK 信号通路、氧化应激(OS)和细胞发育的关系,突出了 MAPK 作为关键介质的作用。单细胞转录组学进一步揭示了间充质细胞中 MAPK 的异常激活。随后在人类胚胎腭间充质细胞(HEPM)中进行的研究证实了类似的生长抑制、细胞凋亡和OS模式,并强调了这些生物标志物的跨物种一致性以及MAPK信号通路的过度激活。通过对 HEPM 细胞进行全面的三组学分析,确定了 MAPK 通路中的关键基因、蛋白质和代谢物。这项开创性的跨物种多组学研究揭示了与TS诱导的颅面发育毒性相关的新型生物标记物和MAPK通路扰动,促进了创新性临床预测、诊断和干预策略的制定,以解决TS诱导的颅面畸形问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
CiteScore
12.10
自引率
5.90%
发文量
1234
审稿时长
88 days
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.
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