解读肝脏中年龄依赖性ECM重塑:蛋白质组学分析及其对衰老和治疗靶点的影响。

IF 5.6 1区 生物学 Q2 CELL BIOLOGY
Juan Liu, Qingru Song, Chen Li, Jiexin Yan, Ni An, Wenzhen Yin, Jinmei Diao, Yuxin Su, Yunfang Wang
{"title":"解读肝脏中年龄依赖性ECM重塑:蛋白质组学分析及其对衰老和治疗靶点的影响。","authors":"Juan Liu, Qingru Song, Chen Li, Jiexin Yan, Ni An, Wenzhen Yin, Jinmei Diao, Yuxin Su, Yunfang Wang","doi":"10.1111/cpr.70087","DOIUrl":null,"url":null,"abstract":"<p><p>Aging is characterised by progressive structural and functional changes in the liver, with the extracellular matrix (ECM) playing a key role in modulating these changes. Our study presents a comprehensive proteomic analysis of the liver ECM across different age stages, uncovering significant age-related changes. Through the identification of 158 ECM proteins in decellularised rat liver scaffolds, we reveal the intricate relationship between ECM composition and liver maturation, as well as the decrease in regenerative capacity. Lumican was identified as a critical regulator with heightened expression in neonatal livers, which is associated with enhanced hepatocyte proliferation and maintenance of stem cell characteristics. Temporal expression analysis distinguished four distinct clusters of ECM proteins, each reflecting the liver's functional evolution from early development to old age. Early developmental stages were marked by proteins essential for liver growth, while adulthood was characterised by a robust ECM supporting metabolic functions. Middle age showed a regulatory shift towards protease balance, and later life was associated with haemostasis-related processes. Our findings underscore the multifaceted role of the ECM in liver health and aging, offering potential opportunities for therapeutic intervention to counteract age-induced liver dysfunction. This study provides a foundational understanding of ECM dynamics in liver aging and sets the stage for the development of innovative strategies to mitigate the effects of age-related liver decline.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70087"},"PeriodicalIF":5.6000,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Deciphering Age-Dependent ECM Remodelling in Liver: Proteomic Profiling and Its Implications for Aging and Therapeutic Targets.\",\"authors\":\"Juan Liu, Qingru Song, Chen Li, Jiexin Yan, Ni An, Wenzhen Yin, Jinmei Diao, Yuxin Su, Yunfang Wang\",\"doi\":\"10.1111/cpr.70087\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Aging is characterised by progressive structural and functional changes in the liver, with the extracellular matrix (ECM) playing a key role in modulating these changes. Our study presents a comprehensive proteomic analysis of the liver ECM across different age stages, uncovering significant age-related changes. Through the identification of 158 ECM proteins in decellularised rat liver scaffolds, we reveal the intricate relationship between ECM composition and liver maturation, as well as the decrease in regenerative capacity. Lumican was identified as a critical regulator with heightened expression in neonatal livers, which is associated with enhanced hepatocyte proliferation and maintenance of stem cell characteristics. Temporal expression analysis distinguished four distinct clusters of ECM proteins, each reflecting the liver's functional evolution from early development to old age. Early developmental stages were marked by proteins essential for liver growth, while adulthood was characterised by a robust ECM supporting metabolic functions. Middle age showed a regulatory shift towards protease balance, and later life was associated with haemostasis-related processes. Our findings underscore the multifaceted role of the ECM in liver health and aging, offering potential opportunities for therapeutic intervention to counteract age-induced liver dysfunction. This study provides a foundational understanding of ECM dynamics in liver aging and sets the stage for the development of innovative strategies to mitigate the effects of age-related liver decline.</p>\",\"PeriodicalId\":9760,\"journal\":{\"name\":\"Cell Proliferation\",\"volume\":\" \",\"pages\":\"e70087\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Proliferation\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1111/cpr.70087\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Proliferation","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/cpr.70087","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

衰老的特征是肝脏结构和功能的渐进式变化,细胞外基质(ECM)在调节这些变化中起着关键作用。我们的研究对不同年龄阶段的肝脏ECM进行了全面的蛋白质组学分析,揭示了显著的年龄相关变化。通过鉴定脱细胞大鼠肝支架中的158个ECM蛋白,我们揭示了ECM组成与肝脏成熟以及再生能力下降之间的复杂关系。Lumican被确定为新生儿肝脏中表达升高的关键调节因子,这与肝细胞增殖增强和干细胞特征维持有关。时间表达分析区分出四个不同的ECM蛋白簇,每个簇都反映了肝脏从早期发育到老年的功能进化。早期发育阶段的特征是肝脏生长必需的蛋白质,而成年期的特征是强大的ECM支持代谢功能。中年表现出向蛋白酶平衡的调节转变,晚年与止血相关的过程有关。我们的研究结果强调了ECM在肝脏健康和衰老中的多方面作用,为治疗干预对抗年龄引起的肝功能障碍提供了潜在的机会。本研究提供了对肝脏衰老中ECM动力学的基本理解,并为开发创新策略以减轻与年龄相关的肝脏衰退的影响奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Deciphering Age-Dependent ECM Remodelling in Liver: Proteomic Profiling and Its Implications for Aging and Therapeutic Targets.

Aging is characterised by progressive structural and functional changes in the liver, with the extracellular matrix (ECM) playing a key role in modulating these changes. Our study presents a comprehensive proteomic analysis of the liver ECM across different age stages, uncovering significant age-related changes. Through the identification of 158 ECM proteins in decellularised rat liver scaffolds, we reveal the intricate relationship between ECM composition and liver maturation, as well as the decrease in regenerative capacity. Lumican was identified as a critical regulator with heightened expression in neonatal livers, which is associated with enhanced hepatocyte proliferation and maintenance of stem cell characteristics. Temporal expression analysis distinguished four distinct clusters of ECM proteins, each reflecting the liver's functional evolution from early development to old age. Early developmental stages were marked by proteins essential for liver growth, while adulthood was characterised by a robust ECM supporting metabolic functions. Middle age showed a regulatory shift towards protease balance, and later life was associated with haemostasis-related processes. Our findings underscore the multifaceted role of the ECM in liver health and aging, offering potential opportunities for therapeutic intervention to counteract age-induced liver dysfunction. This study provides a foundational understanding of ECM dynamics in liver aging and sets the stage for the development of innovative strategies to mitigate the effects of age-related liver decline.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
期刊介绍: Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信