Wuming Qin, Xiaobo Yang, Lu Zhang, Linghui Cao, Shi Ouyang, Dafeng Yang, Yangzhao Zhou, Anji Chen, Tao Liao, Xinyu Zhu, Yuting Liu, Wei Tang, Tongtong Ma, Yiyue Tang, Yonghe Ding, Yun Deng
{"title":"在斑马鱼中,lim1的缺失通过激活gp130/Jak1/Stat3通路导致心脏重构异常和心力衰竭。","authors":"Wuming Qin, Xiaobo Yang, Lu Zhang, Linghui Cao, Shi Ouyang, Dafeng Yang, Yangzhao Zhou, Anji Chen, Tao Liao, Xinyu Zhu, Yuting Liu, Wei Tang, Tongtong Ma, Yiyue Tang, Yonghe Ding, Yun Deng","doi":"10.1016/j.jgg.2025.04.003","DOIUrl":null,"url":null,"abstract":"<p><p>LIM zinc finger domain containing 1 (LIMS1), an evolutionally conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6000,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Loss of lims1 causes aberrant cardiac remodeling and heart failure via activating gp130/Jak1/Stat3 pathway in zebrafish.\",\"authors\":\"Wuming Qin, Xiaobo Yang, Lu Zhang, Linghui Cao, Shi Ouyang, Dafeng Yang, Yangzhao Zhou, Anji Chen, Tao Liao, Xinyu Zhu, Yuting Liu, Wei Tang, Tongtong Ma, Yiyue Tang, Yonghe Ding, Yun Deng\",\"doi\":\"10.1016/j.jgg.2025.04.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>LIM zinc finger domain containing 1 (LIMS1), an evolutionally conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.</p>\",\"PeriodicalId\":54825,\"journal\":{\"name\":\"Journal of Genetics and Genomics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2025-04-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Genetics and Genomics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jgg.2025.04.003\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Genetics and Genomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jgg.2025.04.003","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Loss of lims1 causes aberrant cardiac remodeling and heart failure via activating gp130/Jak1/Stat3 pathway in zebrafish.
LIM zinc finger domain containing 1 (LIMS1), an evolutionally conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.
期刊介绍:
The Journal of Genetics and Genomics (JGG, formerly known as Acta Genetica Sinica ) is an international journal publishing peer-reviewed articles of novel and significant discoveries in the fields of genetics and genomics. Topics of particular interest include but are not limited to molecular genetics, developmental genetics, cytogenetics, epigenetics, medical genetics, population and evolutionary genetics, genomics and functional genomics as well as bioinformatics and computational biology.