已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Hypoxia and STAT3 signalling interactions regulate pro-inflammatory pathways in rheumatoid arthritis

车站3 小干扰RNA 免疫印迹 医学 STAT蛋白 缺氧(环境) 癌症研究 分子生物学 信号转导 细胞培养 化学 转染 生物 细胞生物学 生物化学 遗传学 有机化学 氧气 基因
作者
Wei Gao,Jennifer McCormick,M. Kari Connolly,Emese Balogh,Douglas J. Veale,Ursula Fearon
出处
期刊:Annals of the Rheumatic Diseases [BMJ]
卷期号:74 (6): 1275-1283 被引量:133
标识
DOI:10.1136/annrheumdis-2013-204105
摘要

Objective To examine the effect of hypoxia on Signal Transducer and Activator of Transcription 3 (STAT3)-induced pro-inflammatory pathways in rheumatoid arthritis (RA). Methods Detection of phospho-STAT3 was assessed in RA synovial tissue and fibroblasts (RASFC) by immunohistology/immunofluorescence. Primary RASFCs and a normal synoviocyte cell line (K4IM) were cultured under hypoxic and normoxic conditions±Stat3-siRNA, HIF-siRNA or WP1066 (JAK2-inhibitor). HIF1α, p-STAT3, p-STAT1 and Notch-1IC protein expression were analysed by western blot. Functional mechanisms were quantified by invasion chamber, matrigel and migration assays. IL-6, IL-8, IL-10 and matrixmetalloproteinases (MMP)-3 were quantified by ELISA. Notch-1 receptor, its DLL-4 ligand and downstream target genes ( hrt-1 , hrt-2 ) were quantified by real-time PCR. The effect of WP1066 on spontaneous secretion of pro/anti-inflammatory cytokines and Notch signalling was examined in RA synovial explants ex vivo. Results p-STAT3 was increased in RA synovium compared with control (p<0.05). Hypoxia induced p-STAT3, p-STAT1 and HIF1α expression, an effect blocked by Stat3-siRNA and WP1066. Hypoxia-induced cell invasion, migration and cytokine production were inhibited by Stat3-siRNA (p<0.05) and WP1066 (p<0.05). While HIF1α siRNA inhibited hypoxia-induced p-STAT3 detection, Stat3-siRNA also inhibited hypoxia-induced HIF1α. Furthermore, hypoxia-induced Notch-1IC, DLL4, hrt-1 and -2 expression were significantly inhibited by WP1066 (p<0.05). Finally, in RA synovial explant cultures ex vivo, WP1066 decreased spontaneous secretion of IL-6, IL-8 and MMP3 (p<0.05), Notch-1 mRNA (p<0.05) and induced IL-10 (p<0.05). Conclusions This is the first study to provide evidence of a functional link between HIF1α, STAT3 and Notch-1 signalling in the regulation of pro-inflammatory mechanisms in RA, and further supports a role for STAT blockade in the treatment of RA.
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
富贵儿完成签到 ,获得积分10
1秒前
1秒前
lzm完成签到,获得积分20
2秒前
3秒前
vera完成签到 ,获得积分10
4秒前
4秒前
5秒前
科研小裴完成签到 ,获得积分10
6秒前
8秒前
MchemG应助Karol采纳,获得10
9秒前
9秒前
miles发布了新的文献求助10
9秒前
Rondab应助lzm采纳,获得10
10秒前
CipherSage应助十四采纳,获得10
11秒前
稳重怀蕊发布了新的文献求助10
12秒前
天天快乐应助马尔斯采纳,获得10
13秒前
兜里全是糖完成签到,获得积分10
14秒前
16秒前
一介尘埃完成签到 ,获得积分10
16秒前
CodeCraft应助mmmmm采纳,获得10
18秒前
wang发布了新的文献求助10
18秒前
斯文的难破完成签到 ,获得积分10
19秒前
20秒前
温柔烧鹅发布了新的文献求助10
21秒前
22秒前
23秒前
冷风完成签到 ,获得积分10
25秒前
马尔斯发布了新的文献求助10
25秒前
pumpkin完成签到,获得积分10
26秒前
古道小七完成签到,获得积分10
27秒前
Ramer556发布了新的文献求助10
28秒前
pumpkin发布了新的文献求助10
29秒前
领导范儿应助温柔烧鹅采纳,获得10
37秒前
LJC完成签到,获得积分10
38秒前
Ramer556完成签到,获得积分10
40秒前
40秒前
40秒前
负责怀莲发布了新的文献求助10
41秒前
夏夏完成签到 ,获得积分10
46秒前
46秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
Aktuelle Entwicklungen in der linguistischen Forschung 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989868
求助须知:如何正确求助?哪些是违规求助? 3531994
关于积分的说明 11255752
捐赠科研通 3270793
什么是DOI,文献DOI怎么找? 1805053
邀请新用户注册赠送积分活动 882215
科研通“疑难数据库(出版商)”最低求助积分说明 809208