Proteomic landscape of the extracellular matrix in the fibrotic kidney

细胞外基质 纤维连接蛋白 化学 细胞生物学 生物
作者
Li Li,Meizhi He,Xiaoman Tang,Junxin Huang,Jing Li,Hong Xue,Haiyan Fu,Youhua Liu
出处
期刊:Kidney International [Elsevier]
卷期号:103 (6): 1063-1076 被引量:18
标识
DOI:10.1016/j.kint.2023.01.021
摘要

The extracellular matrix (ECM) is a complex three-dimensional network of proteins surrounding cells, forming a niche that controls cell adhesion, proliferation, migration and differentiation. The ECM network provides an architectural scaffold for surrounding cells and undergoes dynamic changes in composition and contents during the evolution of chronic kidney disease (CKD). Here, we unveiled the proteomic landscape of the ECM by delineating proteome-wide and ECM-specific alterations in normal and fibrotic kidneys. Decellularized kidney tissue scaffolds were made and subjected to proteomic profiling by liquid chromatography with tandem mass spectrometry. A total of 172 differentially expressed proteins were identified in these scaffolds from mice with CKD. Through bioinformatics analysis and experimental validation, we identified a core set of nine signature proteins, which could play a role in establishing an oxidatively stressed, profibrotic, proinflammatory and antiangiogenetic microenvironment. Among these nine proteins, glutathione peroxidase 3 (GPX3) was the only protein with downregulated expression during CKD. Knockdown of GPX3 in vivo augmented ECM expression and aggravated kidney fibrotic lesions after obstructive injury. Transcriptomic profiling revealed that GPX3 depletion resulted in an altered expression of the genes enriched in hypoxia pathway. Knockdown of GPX3 induced NADPH oxidase 2 expression, promoted kidney generation of reactive oxygen species and activated p38 mitogen-activated protein kinase. Conversely, overexpression of exogenous GPX3 alleviated kidney fibrosis, inhibited NADPH oxidase 2 and p38 mitogen-activated protein kinase. These findings suggest that oxidative stress is a pivotal element of the fibrogenic microenvironment. Thus, our studies represent a comprehensive proteomic characterization of the ECM in the fibrotic kidney and provide novel insights into molecular composition of the fibrogenic microenvironment.
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
刚刚
wshwx完成签到,获得积分10
2秒前
5秒前
5秒前
6秒前
6秒前
6秒前
冷静的肖恩完成签到 ,获得积分10
6秒前
善良起眸完成签到 ,获得积分10
7秒前
狂野书易完成签到,获得积分10
9秒前
贾不可发布了新的文献求助10
11秒前
万崽秋秋糖完成签到 ,获得积分10
12秒前
12秒前
李堃完成签到,获得积分10
12秒前
12秒前
13秒前
Rachel发布了新的文献求助10
15秒前
Sarah悦发布了新的文献求助10
16秒前
17秒前
肖亚鑫发布了新的文献求助10
22秒前
贺小刚发布了新的文献求助100
24秒前
狂野大雄鹰完成签到 ,获得积分10
24秒前
24秒前
简体了再说完成签到,获得积分20
24秒前
大米完成签到,获得积分10
26秒前
FreeRice发布了新的文献求助10
27秒前
威武的匕完成签到,获得积分10
27秒前
莫华龙发布了新的文献求助10
28秒前
hihi发布了新的文献求助10
28秒前
29秒前
Ava应助一念之间采纳,获得10
29秒前
无花果应助科研通管家采纳,获得10
30秒前
liaoliaoliao发布了新的文献求助10
31秒前
31秒前
乐乐应助xx采纳,获得10
33秒前
33秒前
科研通AI2S应助Shuo Yang采纳,获得10
33秒前
乐风完成签到,获得积分10
34秒前
lyp7028完成签到,获得积分10
35秒前
爆米花应助Jx采纳,获得10
35秒前
高分求助中
Sustainability in Tides Chemistry 2800
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
China's Relations With Japan 1945-83: The Role of Liao Chengzhi 400
Classics in Total Synthesis IV 400
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 3148072
求助须知:如何正确求助?哪些是违规求助? 2799096
关于积分的说明 7833514
捐赠科研通 2456285
什么是DOI,文献DOI怎么找? 1307194
科研通“疑难数据库(出版商)”最低求助积分说明 628077
版权声明 601655