Novel formononetin-7-sal ester ameliorates pulmonary fibrosis via MEF2c signaling pathway

肺纤维化 博莱霉素 纤维化 MEF2C公司 癌症研究 波形蛋白 信号转导 体内 化学 医学 病理 生物 细胞生物学 内科学 转录因子 免疫组织化学 生物化学 基因 生物技术 化疗
作者
Xueying Zhao,Guiwu Qu,Chenguang Song,Rongrong Li,Weili Liu,Changjun Lv,Xiaodong Song,Jinjin Zhang,Minge Li
出处
期刊:Toxicology and Applied Pharmacology [Elsevier]
卷期号:356: 15-24 被引量:12
标识
DOI:10.1016/j.taap.2018.07.005
摘要

Pulmonary fibrosis is a progressive disorder with poor prognosis and limited treatment options. Therefore, novel therapeutic drugs should be developed in preclinical studies. In this study, we designed and synthesized a novel compound named formononetin-7-sal ester (FS). We also investigated its anti-pulmonary fibrosis ability on transforming growth factor beta 1 (TGF-β1)-stimulated pulmonary epithelial cells and fibroblasts in vitro and on bleomycin (BLM)-induced pulmonary fibrosis in vivo. FS strongly blocked cell proliferation and migration, which were activated by TGF-β1, thereby reducing the expression of lung fibrosis markers, such as vimentin, alpha-smooth muscle actin (α-SMA), Snail, and collagen I and III, and increasing the expression of the epithelial cell marker E-cadherin. FS ameliorated BLM-induced pulmonary fibrosis in mice and decreased histopathologic fibrosis scores and collagen deposition. A low expression of hydroxyproline, vimentin, α-SMA, and Snail and a high expression of E-cadherin were found in FS-treated lungs compared with BLM-instilled lungs. Using the Cignal Finder 45-Pathway Reporter Array, we tested the regulation of FS in pulmonary fibrosis-associated signaling pathways and observed that FS significantly inhibited the myocyte enhancer factor-2c (MEF2c) signaling pathway. Gain- and loss-of-function studies, rescue experiments and promoter activity testing were designed to further confirm this result in vivo and in vitro. Collectively, our results demonstrated that FS prevents pulmonary fibrosis via the MEF2c signaling pathway.
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
大半个菜鸟完成签到,获得积分20
刚刚
1秒前
3秒前
幸福书琴完成签到 ,获得积分10
4秒前
4秒前
vision0000完成签到,获得积分10
4秒前
5秒前
越红完成签到,获得积分10
6秒前
6秒前
开朗紫完成签到,获得积分20
7秒前
cream发布了新的文献求助10
8秒前
FangyingTang完成签到 ,获得积分10
8秒前
10秒前
听海发布了新的文献求助10
11秒前
15秒前
16秒前
冯婷完成签到 ,获得积分10
18秒前
听海完成签到,获得积分10
19秒前
cream关注了科研通微信公众号
20秒前
doby发布了新的文献求助30
21秒前
lonemen应助科研通管家采纳,获得10
22秒前
乐乐应助科研通管家采纳,获得10
22秒前
上官若男应助科研通管家采纳,获得10
22秒前
顾矜应助科研通管家采纳,获得10
22秒前
carpsz应助科研通管家采纳,获得10
22秒前
NexusExplorer应助科研通管家采纳,获得10
22秒前
完美世界应助科研通管家采纳,获得10
23秒前
SciGPT应助科研通管家采纳,获得10
23秒前
23秒前
tanjianxin应助科研通管家采纳,获得10
23秒前
Zer完成签到,获得积分10
23秒前
学习爱我发布了新的文献求助10
24秒前
12完成签到 ,获得积分10
24秒前
24秒前
25秒前
斯文败类应助小于一采纳,获得10
25秒前
26秒前
可靠代丝完成签到,获得积分10
27秒前
机智的天蓉完成签到,获得积分10
27秒前
QY11发布了新的文献求助10
28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
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Le dégorgement réflexe des Acridiens 800
Defense against predation 800
Very-high-order BVD Schemes Using β-variable THINC Method 568
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 3136300
求助须知:如何正确求助?哪些是违规求助? 2787372
关于积分的说明 7781210
捐赠科研通 2443353
什么是DOI,文献DOI怎么找? 1299108
科研通“疑难数据库(出版商)”最低求助积分说明 625349
版权声明 600939