Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis

细胞外基质 巨噬细胞 组织蛋白酶 基质(化学分析) 化学 生物 细胞生物学 生物化学 体外 色谱法
作者
Tao Zuo,Qi Xie,Jinfang Liu,Jing Yang,Jiahui Shi,Degang Kong,Yin Wang,Zhenpeng Zhang,Huixia Gao,Daobing Zeng,Xinxin Wang,Tao Ping,Wei Wei,Jun Wang,Yuan Li,Qi Long,Chonghui Li,Lei Chang,Huimin Ning,Yanchang Li,Chun‐Ping Cui,Xinlan Ge,Jushan Wu,Guangming Li,Xuechuan Hong,Xiao Yang,Erhei Dai,Fuchu He,Junzhu Wu,Yuanyuan Ruan,Shichun Lu,Ping Xu
出处
期刊:Gastroenterology [Elsevier]
卷期号:165 (3): 746-761.e16 被引量:14
标识
DOI:10.1053/j.gastro.2023.05.039
摘要

Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis.We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis.We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5β1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models.CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
完美世界应助dd采纳,获得10
刚刚
廉凌波发布了新的文献求助10
1秒前
干净的烧鹅完成签到,获得积分10
2秒前
2秒前
setmefree发布了新的文献求助10
3秒前
阿杰发布了新的文献求助10
4秒前
5秒前
科研通AI2S应助111采纳,获得10
6秒前
小巧亦竹完成签到,获得积分10
6秒前
浮生发布了新的文献求助10
7秒前
sweetsev7n关注了科研通微信公众号
7秒前
WW发布了新的文献求助10
7秒前
qaq完成签到,获得积分10
8秒前
kkssrrrr完成签到 ,获得积分10
8秒前
zhangst发布了新的文献求助10
10秒前
Eva完成签到,获得积分10
12秒前
李健的小迷弟应助青炀采纳,获得10
14秒前
15秒前
zhangst完成签到,获得积分10
16秒前
优雅静枫发布了新的文献求助10
18秒前
科研修沟发布了新的文献求助10
18秒前
领导范儿应助lll采纳,获得10
19秒前
Estrella应助Christina采纳,获得10
19秒前
20秒前
21秒前
21秒前
sweetsev7n发布了新的文献求助20
22秒前
容止完成签到 ,获得积分10
22秒前
22秒前
23秒前
我是老大应助WW采纳,获得10
23秒前
狗蛋完成签到 ,获得积分10
24秒前
小白完成签到,获得积分10
24秒前
25秒前
淡淡菠萝发布了新的文献求助10
25秒前
111发布了新的文献求助10
26秒前
林夏发布了新的文献求助10
26秒前
假面绅士发布了新的文献求助10
26秒前
Ginger发布了新的文献求助10
27秒前
失眠思雁发布了新的文献求助30
28秒前
高分求助中
The Oxford Handbook of Social Cognition (Second Edition, 2024) 1050
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Chen Hansheng: China’s Last Romantic Revolutionary 500
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 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 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3140687
求助须知:如何正确求助?哪些是违规求助? 2791539
关于积分的说明 7799401
捐赠科研通 2447880
什么是DOI,文献DOI怎么找? 1302124
科研通“疑难数据库(出版商)”最低求助积分说明 626459
版权声明 601194