Dong Feng, Yanhan Dong, Yiran Song, Nicholas Yapundich, Yifang Xie, Brian Spurlock, Tingting Lyu, Landry Kuehn, Li Qian, Jiandong Liu
{"title":"Nr4a1调节斑马鱼的炎症和心脏再生。","authors":"Dong Feng, Yanhan Dong, Yiran Song, Nicholas Yapundich, Yifang Xie, Brian Spurlock, Tingting Lyu, Landry Kuehn, Li Qian, Jiandong Liu","doi":"10.1242/dev.204395","DOIUrl":null,"url":null,"abstract":"<p><p>Recent findings have highlighted the complex role of inflammation in zebrafish heart regeneration, demonstrating that although inflammation is essential for initiating transient fibrosis and tissue repair, chronic inflammation, and unresolved fibrosis, could impede full regenerative recovery. In this study, we identified the nuclear receptor Nr4a1 as a crucial regulator of this regenerative process in zebrafish. Loss of Nr4a1 function led to a prolonged and excessive inflammatory response, disrupted neutrophil migration, delayed fibrin clearance, and ultimately impaired heart regeneration. Transcriptome-wide RNA-seq analysis at different injury stages revealed molecular disruptions associated with dysregulated inflammation and fibrosis in nr4a1 mutants. Notably, partial inhibition of the pro-inflammatory cytokine Tnfα rescued heart regeneration in the nr4a1 mutants, highlighting the therapeutic potential of modulating inflammation. Our findings suggest that Nr4a1 plays a crucial role in orchestrating the immune response during heart regeneration and may serve as a valuable target for enhancing cardiac repair following injury.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276807/pdf/","citationCount":"0","resultStr":"{\"title\":\"Nr4a1 modulates inflammation and heart regeneration in zebrafish.\",\"authors\":\"Dong Feng, Yanhan Dong, Yiran Song, Nicholas Yapundich, Yifang Xie, Brian Spurlock, Tingting Lyu, Landry Kuehn, Li Qian, Jiandong Liu\",\"doi\":\"10.1242/dev.204395\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Recent findings have highlighted the complex role of inflammation in zebrafish heart regeneration, demonstrating that although inflammation is essential for initiating transient fibrosis and tissue repair, chronic inflammation, and unresolved fibrosis, could impede full regenerative recovery. In this study, we identified the nuclear receptor Nr4a1 as a crucial regulator of this regenerative process in zebrafish. Loss of Nr4a1 function led to a prolonged and excessive inflammatory response, disrupted neutrophil migration, delayed fibrin clearance, and ultimately impaired heart regeneration. Transcriptome-wide RNA-seq analysis at different injury stages revealed molecular disruptions associated with dysregulated inflammation and fibrosis in nr4a1 mutants. Notably, partial inhibition of the pro-inflammatory cytokine Tnfα rescued heart regeneration in the nr4a1 mutants, highlighting the therapeutic potential of modulating inflammation. Our findings suggest that Nr4a1 plays a crucial role in orchestrating the immune response during heart regeneration and may serve as a valuable target for enhancing cardiac repair following injury.</p>\",\"PeriodicalId\":11375,\"journal\":{\"name\":\"Development\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276807/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Development\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1242/dev.204395\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/dev.204395","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/11 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
Nr4a1 modulates inflammation and heart regeneration in zebrafish.
Recent findings have highlighted the complex role of inflammation in zebrafish heart regeneration, demonstrating that although inflammation is essential for initiating transient fibrosis and tissue repair, chronic inflammation, and unresolved fibrosis, could impede full regenerative recovery. In this study, we identified the nuclear receptor Nr4a1 as a crucial regulator of this regenerative process in zebrafish. Loss of Nr4a1 function led to a prolonged and excessive inflammatory response, disrupted neutrophil migration, delayed fibrin clearance, and ultimately impaired heart regeneration. Transcriptome-wide RNA-seq analysis at different injury stages revealed molecular disruptions associated with dysregulated inflammation and fibrosis in nr4a1 mutants. Notably, partial inhibition of the pro-inflammatory cytokine Tnfα rescued heart regeneration in the nr4a1 mutants, highlighting the therapeutic potential of modulating inflammation. Our findings suggest that Nr4a1 plays a crucial role in orchestrating the immune response during heart regeneration and may serve as a valuable target for enhancing cardiac repair following injury.
期刊介绍：
Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication.
To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
