USP5‐Rich Apoptotic Extracellular Vesicles Regulate Nucleus Pulposus Cells Apoptosis and DNA Damage Repair by Preventing E2F1 Proteasomal Degradation

细胞生物学 细胞凋亡 间充质干细胞 生物 移植 DNA损伤 脱氮酶 干细胞 泛素 再生医学 DNA修复 程序性细胞死亡 癌症研究 化学 DNA 生物化学 医学 外科 基因
作者
Pengzhi Shi,Haiyang Gao,Zhangrong Cheng,Wenbo Wu,Anran Zhang,Xiang‐Long Chen,Wu Wang,Yukun Zhang
出处
期刊:Journal of extracellular vesicles [Taylor & Francis]
卷期号:14 (8)
标识
DOI:10.1002/jev2.70148
摘要

ABSTRACT Mesenchymal stem cell (MSC) transplantation is considered one of the most promising regenerative strategies for treating degenerative musculoskeletal diseases, yet its underlying therapeutic mechanisms remain incompletely understood. In this study, we demonstrate that transplanted MSCs regulate apoptosis and DNA damage repair (DDR) in senescent nucleus pulposus cells (NPCs) by releasing apoptotic extracellular vesicles (ApoEVs), thereby delaying the process of intervertebral disc degeneration (IVDD). Mechanistically, we found that NPCs in degenerated discs exhibit abnormal subcellular localization of the deubiquitinase ubiquitin specific peptidase 5 (USP5), with excessive cytoplasmic retention leading to aberrant ubiquitination and degradation of the E2F transcription factor 1 (E2F1). Following transplantation into the degenerative disc microenvironment, MSCs undergo extensive apoptosis in the short‐term and release ApoEVs enriched in highly acetylated USP5. These vesicles promote nuclear translocation of USP5 in NPCs, which stabilizes E2F1 by preventing its ubiquitin‐mediated degradation. This cascade reduces DNA damage and apoptosis in NPCs and enhances their functional activity. Overall, our findings reveal a previously unrecognized mechanism by which apoptotic donor MSCs exert therapeutic effects through intercellular communication, specifically by modulating recipient NPCs apoptosis and DDR pathways. This study underscores the critical role of donor cell apoptosis in the therapeutic efficacy of stem cell transplantation and provides new insights for optimizing regenerative medicine strategies.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
litpand完成签到 ,获得积分0
1秒前
1秒前
2秒前
3秒前
大气如雪完成签到 ,获得积分10
4秒前
4秒前
5秒前
5秒前
共享精神应助兴奋的白凝采纳,获得10
5秒前
CG1234567发布了新的文献求助10
6秒前
lhy发布了新的文献求助10
6秒前
mch完成签到,获得积分10
7秒前
PENGDOCTOR完成签到,获得积分10
7秒前
余晓发布了新的文献求助10
8秒前
9秒前
量子星尘发布了新的文献求助10
9秒前
科研通AI6应助土豆淀粉采纳,获得10
10秒前
10秒前
11秒前
11秒前
rues011完成签到 ,获得积分10
12秒前
浮游应助tguczf采纳,获得10
12秒前
llfire完成签到,获得积分10
14秒前
11完成签到,获得积分10
14秒前
14秒前
15秒前
yc发布了新的文献求助10
15秒前
15秒前
16秒前
rues011关注了科研通微信公众号
16秒前
lv发布了新的文献求助30
16秒前
复杂鸭子完成签到,获得积分10
17秒前
斯文败类应助七庙采纳,获得10
17秒前
18秒前
fred完成签到,获得积分10
18秒前
顾矜应助CG1234567采纳,获得10
18秒前
18秒前
东堂完成签到,获得积分10
19秒前
庾天磊完成签到,获得积分10
19秒前
19秒前
高分求助中
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Zeolites: From Fundamentals to Emerging Applications 1500
Architectural Corrosion and Critical Infrastructure 1000
Early Devonian echinoderms from Victoria (Rhombifera, Blastoidea and Ophiocistioidea) 1000
By R. Scott Kretchmar - Practical Philosophy of Sport and Physical Activity - 2nd (second) Edition: 2nd (second) Edition 666
Energy-Size Reduction Relationships In Comminution 500
Principles Of Comminution, I-Size Distribution And Surface Calculations 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 内科学 生物化学 物理 计算机科学 纳米技术 遗传学 基因 复合材料 化学工程 物理化学 病理 催化作用 免疫学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 4941396
求助须知:如何正确求助?哪些是违规求助? 4207446
关于积分的说明 13077705
捐赠科研通 3986303
什么是DOI,文献DOI怎么找? 2182555
邀请新用户注册赠送积分活动 1198146
关于科研通互助平台的介绍 1110389