Fenofibrate inhibits MOXD1 and PDZK1IP1 expression and improves lipid deposition and inflammation in mice with alcoholic fatty liver

非诺贝特 酒精性肝病 炎症 基因沉默 过氧化物酶体增殖物激活受体 氧化应激 脂肪肝 癌症研究 化学 医学 肝硬化 药理学 受体 内科学 基因 生物化学 疾病
作者
Tongtong Pan,Zhiguang Zhao,Jianshuang Lu,Hong Wen,Jiarong Zhang,Yali Xu,Yongping Chen,Xiaoya Jin
出处
期刊:Life Sciences [Elsevier]
卷期号:336: 122321-122321
标识
DOI:10.1016/j.lfs.2023.122321
摘要

Alcoholic liver disease (ALD) can develop into cirrhosis and hepatocellular carcinoma but no specific drugs are available. Fenofibrate is therapeutically effective in ALD, however, the exact mechanism remains unknown. We explored the hub genes of ALD and the role of fenofibrate in ALD.The hub genes of ALD were screened by bioinformatics method, and their functional enrichment, signalling pathways, target genes and their correlation with immune microenvironment and pathogenic genes were analysed. We also analysed the binding affinity of fenofibrate to proteins of hub genes using molecular docking techniques, and the effects on hub gene expression, lipid deposition, oxidative stress and inflammation in the liver of National Institute on Alcohol Abuse and Alcoholism (NIAAA) model mice. The regulatory effects of fenofibrate on MOXD1 and PDZK1P1 were investigated after gene silencing of peroxisome proliferator-activated receptor-α (Ppar-α).Hub genes identified, including monooxygenase DBH-like 1 (MOXD1), PDZK1-interacting protein 1 (PDZK1IP1) and solute carrier 51 β (SLC51B), are highly predictive for ALD. Hepatic MOXD1 and PDZK1IP1 expression was elevated in patients with ALD and NIAAA model mice, with no significant difference in SLC51B expression between the groups. Fenofibrate binds tightly to MOXD1 and PDZK1IP1, inhibits their hepatic expression independently of PPAR-α signalling, and ameliorates lipid deposition, oxidative stress and inflammatory responses in NIAAA model mice.MOXD1 and PDZK1IP1 are key genes in ALD progression; fenofibrate improves liver damage in NIAAA model mice by downregulating their expression. Our findings provide insight for improving diagnostic and therapeutic strategies for ALD.
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
kchrisuzad发布了新的文献求助30
2秒前
托塔小姐发布了新的文献求助10
3秒前
华仔应助zr237618采纳,获得10
3秒前
冷傲书萱应助LYB吕采纳,获得10
3秒前
飘柔完成签到,获得积分20
4秒前
4秒前
5秒前
NexusExplorer应助IAMXC采纳,获得10
5秒前
5秒前
向前完成签到,获得积分10
5秒前
长情伊应助明亮的涵山采纳,获得10
6秒前
李杰发布了新的文献求助10
6秒前
6秒前
李爱国应助内向忆南采纳,获得10
6秒前
wenny完成签到,获得积分10
7秒前
8秒前
无心的枫完成签到 ,获得积分10
8秒前
8秒前
开心草丛完成签到 ,获得积分10
10秒前
Owen应助bvuiragybv采纳,获得10
10秒前
粘豆包完成签到 ,获得积分10
10秒前
哇咔咔发布了新的文献求助10
10秒前
Frank发布了新的文献求助10
10秒前
禾禾完成签到,获得积分10
10秒前
10秒前
12秒前
12秒前
13秒前
开心草丛关注了科研通微信公众号
13秒前
123发布了新的文献求助10
14秒前
kchrisuzad发布了新的文献求助10
14秒前
CipherSage应助美君采纳,获得10
17秒前
18秒前
大宋发布了新的文献求助10
18秒前
jingtanhao发布了新的文献求助10
19秒前
chyx完成签到,获得积分20
20秒前
斯文败类应助kyfw采纳,获得10
20秒前
20秒前
bkagyin应助南部之星琪采纳,获得10
21秒前
21秒前
高分求助中
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Chen Hansheng: China’s Last Romantic Revolutionary 500
COSMETIC DERMATOLOGY & SKINCARE PRACTICE 388
Case Research: The Case Writing Process 300
Global Geological Record of Lake Basins 300
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 3141883
求助须知:如何正确求助?哪些是违规求助? 2792846
关于积分的说明 7804392
捐赠科研通 2449137
什么是DOI,文献DOI怎么找? 1303086
科研通“疑难数据库(出版商)”最低求助积分说明 626769
版权声明 601265