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!

Activation of PI3K in response to high glucose leads to regulation of SOCS-3 and STAT1/3 signals and induction of glomerular mesangial extracellular matrix formation

系膜细胞 医学 细胞外基质 车站3 信号转导 肾小球硬化 PI3K/AKT/mTOR通路 内科学 化学 癌症研究 细胞生物学 生物 蛋白尿
作者
Meei‐Ling Sheu,Chin-Chang Shen,Jia-Rong Jheng,Chih‐Kang Chiang
出处
期刊:Oncotarget [Impact Journals LLC]
卷期号:8 (10): 16925-16938 被引量:15
标识
DOI:10.18632/oncotarget.14808
摘要

// Meei-Ling Sheu 1, 2, 3, * , Chin-Chang Shen 4, * , Jia-Rong Jheng 5, 6 , Chih-Kang Chiang 5, 6, 7 1 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan 2 Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan 3 Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan 4 Chemical Engineering Division, Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan 5 Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan 6 Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan 7 Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Chih-Kang Chiang, email: ckchiang@ntu.edu.tw Keywords: extracellular matrix, high glucose, mesangial cell, phosphoinositide 3-kinase, signal transduction Received: October 26, 2016 Accepted: December 13, 2016 Published: January 24, 2017 ABSTRACT Excessive deposition of extracellular matrix (ECM) in the glomerulus contributed by mesangial cells is the hallmark of diabetic nephropathy, eventually leading to glomerulosclerosis. In this study, we examined the regulatory signals involved in the high glucose (HG)-induced overproduction of ECM in rat mesangial cells (RMCs). We disclosed excessive fibronectin and collagen IV production, tyrosine phosphorylation of signal transducer and activator of transcription 1 and 3 (STAT1/3), and up-regulation of suppressor of cytokine signaling-3 (SOCS-3) expression in HG-treated RMCs. STAT1/STAT3 binding element was essential for SOCS-3 promoter activity stimulated by HG. HG was capable of promoting the specific DNA binding activities to an oligonucleotide probe containing the SOCS-3 sequence. The selective phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and dominant negative p85 vector (DNΔp85) transfection effectively abolished these HG-induced responses. Moreover, HG markedly increased the cyclin kinase inhibitor p27 Kip1 protein expression, which could be inhibited by LY294002 or transfection of DNΔp85. Taken together, these results suggest that HG-induced SOCS-3 upregulation depends upon the presence of STAT-binding element in the SOCS-3 promoter, which is specifically activated by STAT1/3. The PI3K/STAT1/3 signaling pathway mediated HG-triggered ECM accumulation and SOCS-3 upregulation in RMCs.
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
广州小肥羊完成签到 ,获得积分10
3秒前
皮皮蟹完成签到,获得积分10
7秒前
完美世界应助ceeray23采纳,获得20
12秒前
曾经的电脑完成签到 ,获得积分10
17秒前
Sky完成签到,获得积分10
17秒前
握瑾怀瑜完成签到 ,获得积分0
18秒前
轻松的惜芹应助科研达人采纳,获得10
21秒前
Orange应助高兴的忆曼采纳,获得10
23秒前
平淡访冬完成签到 ,获得积分10
30秒前
jokerhoney完成签到,获得积分10
32秒前
李娇完成签到 ,获得积分10
33秒前
李姝完成签到 ,获得积分10
34秒前
李昕123完成签到 ,获得积分10
36秒前
38秒前
干净涵梅发布了新的文献求助10
43秒前
星辰大海应助大喵采纳,获得10
43秒前
CC发布了新的文献求助10
46秒前
你大米哥完成签到 ,获得积分10
48秒前
asaki完成签到,获得积分10
50秒前
瑞瑞刘完成签到 ,获得积分10
53秒前
freshfire完成签到 ,获得积分10
53秒前
爱吃大米饭完成签到 ,获得积分10
54秒前
59秒前
yx_cheng应助CC采纳,获得30
1分钟前
小鸟芋圆露露完成签到 ,获得积分10
1分钟前
大喵发布了新的文献求助10
1分钟前
传奇3应助滴滴哒采纳,获得10
1分钟前
大喵完成签到,获得积分10
1分钟前
陈一完成签到 ,获得积分10
1分钟前
我是老大应助Li采纳,获得10
1分钟前
一叶完成签到 ,获得积分10
1分钟前
最爱地瓜和虾滑完成签到 ,获得积分10
1分钟前
1分钟前
1分钟前
可爱的函函应助叮当拉卡采纳,获得10
1分钟前
朴实的小萱完成签到,获得积分10
1分钟前
滴滴哒发布了新的文献求助10
1分钟前
今后应助litieniu采纳,获得10
1分钟前
冲冲冲完成签到 ,获得积分10
1分钟前
李健应助科研达人采纳,获得10
1分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
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
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 3990012
求助须知:如何正确求助?哪些是违规求助? 3532047
关于积分的说明 11256141
捐赠科研通 3270918
什么是DOI,文献DOI怎么找? 1805105
邀请新用户注册赠送积分活动 882270
科研通“疑难数据库(出版商)”最低求助积分说明 809216