Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFβ1

心理压抑 糖尿病肾病 医学 转化生长因子 糖尿病 癌症研究 病理 生物 肾病 药理学 内科学 内分泌学 基因表达 基因 生物化学
作者
Pan Gao,Liliang Li,Yang Liu,Dingkun Gui,Jiarong Zhang,Junfeng Han,Jiajia Wang,Niansong Wang,Junxi Lu,Suzhen Chen,Liping Hou,Honglin Sun,Liping Xie,Jian Zhou,Chao Peng,Yan Lu,Xuemei Peng,Cunchuan Wang,Ji Miao,Umut Özcan,Yü Huang,Weiping Jia,Junli Liu
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science (AAAS)]
卷期号:11 (510) 被引量:51
标识
DOI:10.1126/scitranslmed.aaw2050
摘要

Transforming growth factor-β1 (TGFβ1) has been identified as a major pathogenic factor underlying the development of diabetic nephropathy (DN). However, the current strategy of antagonizing TGFβ1 has failed to demonstrate favorable outcomes in clinical trials. To identify a different therapeutic approach, we designed a mass spectrometry-based DNA-protein interaction screen to find transcriptional repressors that bind to the TGFB1 promoter and identified Yin Yang 1 (YY1) as a potent repressor of TGFB1. YY1 bound directly to TGFB1 promoter regions and repressed TGFB1 transcription in human renal mesangial cells. In mouse models, YY1 was elevated in mesangial cells during early diabetic renal lesions and decreased in later stages, and knockdown of renal YY1 aggravated, whereas overexpression of YY1 attenuated glomerulosclerosis. In addition, although their duration of diabetic course was comparable, patients with higher YY1 expression developed diabetic nephropathy more slowly compared to those who presented with lower YY1 expression. We found that a small molecule, eudesmin, suppressed TGFβ1 and other profibrotic factors by increasing YY1 expression in human renal mesangial cells and attenuated diabetic renal lesions in DN mouse models by increasing YY1 expression. These results suggest that YY1 is a potent transcriptional repressor of TGFB1 during the development of DN in diabetic mice and that small molecules targeting YY1 may serve as promising therapies for treating DN.
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
2秒前
红鲤完成签到,获得积分10
3秒前
zyyyy发布了新的文献求助10
4秒前
yyds发布了新的文献求助10
4秒前
dasfdufos发布了新的文献求助10
5秒前
紫伊完成签到,获得积分10
5秒前
9秒前
12秒前
大个应助zyyyy采纳,获得10
14秒前
Lucas应助Elvira采纳,获得10
15秒前
张112233完成签到,获得积分10
15秒前
LI完成签到,获得积分10
17秒前
迪迪完成签到,获得积分10
17秒前
tjpuzhang发布了新的文献求助10
18秒前
pw完成签到 ,获得积分10
19秒前
阳光海云完成签到,获得积分10
20秒前
彭于晏应助牛牛采纳,获得10
21秒前
SciGPT应助dasfdufos采纳,获得30
21秒前
26秒前
危机的寒烟完成签到,获得积分10
30秒前
dasfdufos完成签到,获得积分20
33秒前
从容襄完成签到,获得积分10
34秒前
123完成签到,获得积分10
34秒前
36秒前
38秒前
tourist585应助大方的含桃采纳,获得10
39秒前
39秒前
LL来了完成签到 ,获得积分10
40秒前
青小含发布了新的文献求助10
40秒前
谦让的莆完成签到 ,获得积分10
41秒前
背后的小白菜完成签到,获得积分10
44秒前
威武QY发布了新的文献求助10
45秒前
Akim应助hwezhu采纳,获得10
45秒前
喜东东完成签到 ,获得积分10
46秒前
暴躁的访波完成签到,获得积分10
50秒前
ok关闭了ok文献求助
55秒前
56秒前
迷路山水发布了新的文献求助10
56秒前
老实的半山完成签到,获得积分10
56秒前
高分求助中
Solution Manual for Strategic Compensation A Human Resource Management Approach 1200
Natural History of Mantodea 螳螂的自然史 1000
Glucuronolactone Market Outlook Report: Industry Size, Competition, Trends and Growth Opportunities by Region, YoY Forecasts from 2024 to 2031 800
A Photographic Guide to Mantis of China 常见螳螂野外识别手册 800
Zeitschrift für Orient-Archäologie 500
Autoregulatory progressive resistance exercise: linear versus a velocity-based flexible model 500
The analysis and solution of partial differential equations 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 物理化学 催化作用 细胞生物学 免疫学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3339768
求助须知:如何正确求助?哪些是违规求助? 2967834
关于积分的说明 8631141
捐赠科研通 2647309
什么是DOI,文献DOI怎么找? 1449590
科研通“疑难数据库(出版商)”最低求助积分说明 671464
邀请新用户注册赠送积分活动 660434