<scp>PPARgamma</scp> agonism inhibits progression of premalignant lesions in a murine lung squamous cell carcinoma model

吡格列酮 病理 角蛋白14 癌症研究 发育不良 生物 医学 内分泌学 生物化学 转基因 转基因小鼠 基因 2型糖尿病 糖尿病
作者
Lori D Dwyer-Nield,Debbie G McArthur,Tyler M Hudish,Laura I Hudish,Carol Mirita,Kayla Sompel,Alex J Smith,Kiana Alavi,Moumita Ghosh,Daniel T Merrick,Meredith A Tennis,Robert L Keith
出处
期刊:International Journal of Cancer [Wiley]
卷期号:151 (12): 2195-2205 被引量:1
标识
DOI:10.1002/ijc.34210
摘要

The N-nitroso-trischloroethylurea (NTCU)-induced mouse model of squamous lung carcinoma recapitulates human disease from premalignant dysplasia through invasive tumors, making it suitable for preclinical chemoprevention drug testing. Pioglitazone is a peroxisome proliferator-activated receptor γ (PPARγ) agonist shown to prevent lung tumors in preclinical models. We investigated pioglitazone's effect on lesion development and markers of potential preventive mechanisms in the NTCU model. Female FVB/N mice were exposed to vehicle, NTCU or NTCU + oral pioglitazone for 32 weeks. NTCU induces the appearance of basal cells in murine airways while decreasing/changing their epithelial cell makeup, resulting in development of bronchial dysplasia. H&E and keratin 5 (KRT5) staining were used to detect and grade squamous lesions in formalin fixed lungs. mRNA expression of epithelial to mesenchymal transition (EMT) markers and basal cell markers were measured by qPCR. Dysplasia persistence markers desmoglein 3 and polo like kinase 1 were measured by immunohistochemistry. Basal cell markers KRT14 and p63, club cell specific protein and ciliated cell marker acetylated tubulin were measured by immunofluorescence. Pioglitazone treatment significantly reduced squamous lesions and the presence of airway basal cells, along with increasing normal epithelial cells in the airways of NTCU-exposed mice. Pioglitazone also significantly influenced EMT gene expression to promote a more epithelial, and less mesenchymal, phenotype. Pioglitazone reduced the presence of squamous dysplasia and maintained normal airway cell composition. This work increases the knowledge of mechanistic pathways in PPARγ agonism for lung cancer interception and provides a basis for further investigation to advance this chemoprevention strategy.
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
1秒前
sam发布了新的文献求助10
2秒前
zyt应助meimei采纳,获得10
4秒前
4秒前
巴基斯坦农民完成签到,获得积分20
6秒前
6秒前
完美世界应助夏天采纳,获得10
6秒前
bonnie完成签到,获得积分10
6秒前
CCC完成签到,获得积分10
6秒前
7秒前
TranYan完成签到,获得积分10
7秒前
儒雅一凤完成签到 ,获得积分10
7秒前
在路上完成签到 ,获得积分0
7秒前
酷炫迎波完成签到,获得积分10
9秒前
无足鸟应助复杂的雪巧采纳,获得10
11秒前
万能图书馆应助ccccccc采纳,获得10
11秒前
hhl发布了新的文献求助10
11秒前
西瓜汁完成签到,获得积分10
13秒前
nowfitness完成签到,获得积分10
14秒前
15秒前
zzr完成签到,获得积分10
16秒前
17秒前
顾矜应助1781266采纳,获得10
18秒前
19秒前
hhl完成签到,获得积分10
19秒前
19秒前
岁月如歌完成签到,获得积分10
21秒前
ljs发布了新的文献求助10
21秒前
超超爱吃瓜完成签到,获得积分10
21秒前
十八发布了新的文献求助10
22秒前
22秒前
22秒前
kf033完成签到,获得积分10
24秒前
26秒前
宓不评完成签到 ,获得积分20
27秒前
wanci应助巴基斯坦农民采纳,获得10
29秒前
29秒前
陈秋发布了新的文献求助10
31秒前
乐在奇中完成签到,获得积分10
32秒前
34秒前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Pharmacogenomics: Applications to Patient Care, Third Edition 800
A Dissection Guide & Atlas to the Rabbit 500
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 3082501
求助须知:如何正确求助?哪些是违规求助? 2735655
关于积分的说明 7538441
捐赠科研通 2385263
什么是DOI,文献DOI怎么找? 1264761
科研通“疑难数据库(出版商)”最低求助积分说明 612786
版权声明 597665