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的填写文献信息,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!

Resolution of liver cirrhosis using vitamin A–coupled liposomes to deliver siRNA against a collagen-specific chaperone

肝硬化 小干扰RNA 化学 纤维化 肝星状细胞 癌症研究 维生素 生物化学 生物 药理学 脂质体 医学 内科学 核糖核酸 基因
作者
Yasushi Sato,Kazuyuki Murase,Junji Kato,Masayoshi Kobune,Tsutomu Sato,Yutaka Kawano,Rishu Takimoto,Kouichi Takada,Koji Miyanishi,Takuya Matsunaga,Tetsuji Takayama,Yoshiro Niitsu
出处
期刊:Nature Biotechnology [Springer Nature]
卷期号:26 (4): 431-442 被引量:555
标识
DOI:10.1038/nbt1396
摘要

There are currently no approved antifibrotic therapies for liver cirrhosis. We used vitamin A‐coupled liposomes to deliver small interfering RNA (siRNA) against gp46, the rat homolog of human heat shock protein 47, to hepatic stellate cells. Our approach exploits the key roles of these cells in both fibrogenesis as well as uptake and storage of vitamin A. Five treatments with the siRNA-bearing vitamin A‐coupled liposomes almost completely resolved liver fibrosis and prolonged survival in rats with otherwise lethal dimethylnitrosamine-induced liver cirrhosis in a dose- and duration-dependent manner. Rescue was not related to off-target effects or associated with recruitment of innate immunity. Receptor-specific siRNA delivery was similarly effective in suppressing collagen secretion and treating fibrosis induced by CCl4 or bile duct ligation. The efficacy of the approach using both acute and chronic models of liver fibrosis suggests its therapeutic potential for reversing human liver cirrhosis. Liver cirrhosis, or fibrosis, the ultimate pathological feature of all forms of chronic hepatic damage, is responsible for much morbidity and mortality worldwide. The principal cell type responsible for liver fibrosis is the hepatic stellate (HS) cell, a resident perisinusoidal cell that takes up vitamin A from circulation and stores it. When stimulated by reactive oxygen intermediates or cytokines, HS cells become activated and are transformed to proliferative, fibrogenic and contractile myofibroblasts 1 , which synthesize and secrete procollagen, which accumulates as insoluble collagen after its terminal domains are cleaved by procollagen peptides, causing fibrosis. The collagen-specific chaperone, heat shock protein 47 (HSP47), facilitates collagen secretion by ensuring proper triple-helix formation of procollagen in the endoplasmic reticulum and has also been implicated in translational regulation of procollagen synthesis 2,3 .
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
赵欣完成签到,获得积分10
2秒前
尉迟半芹完成签到,获得积分10
3秒前
爆米花应助ccalvintan采纳,获得10
3秒前
尉迟半芹发布了新的文献求助50
8秒前
Neehi发布了新的文献求助10
11秒前
Duduk完成签到,获得积分10
11秒前
脑洞疼应助啊湫超爱学习采纳,获得10
12秒前
cctv18应助科研通管家采纳,获得10
13秒前
科研通AI2S应助科研通管家采纳,获得10
13秒前
田様应助科研通管家采纳,获得10
14秒前
莫言应助科研通管家采纳,获得10
14秒前
科研通AI2S应助科研通管家采纳,获得10
14秒前
科目三应助科研通管家采纳,获得30
14秒前
SciGPT应助科研通管家采纳,获得10
14秒前
19秒前
shardowzx完成签到,获得积分10
19秒前
shardowzx发布了新的文献求助10
23秒前
翟延恶发布了新的文献求助10
26秒前
lycoris发布了新的文献求助10
26秒前
打打应助小医神僧采纳,获得30
28秒前
YOLO完成签到 ,获得积分10
29秒前
31秒前
隐形曼青应助MishimaErika采纳,获得10
33秒前
冷艳幻珊发布了新的文献求助10
37秒前
bai完成签到,获得积分20
39秒前
39秒前
星辰大海应助CC采纳,获得10
40秒前
打打应助锦鲤采纳,获得10
41秒前
CipherSage应助老八采纳,获得30
45秒前
卡恩完成签到 ,获得积分10
51秒前
木每完成签到,获得积分10
51秒前
lycoris完成签到,获得积分10
55秒前
57秒前
Lett完成签到,获得积分10
58秒前
清爽笑白发布了新的文献求助10
1分钟前
1分钟前
sally完成签到 ,获得积分10
1分钟前
深情安青应助xin采纳,获得10
1分钟前
CipherSage应助周凡淇采纳,获得10
1分钟前
1分钟前
高分求助中
中国国际图书贸易总公司40周年纪念文集 大事记1949-1987 2000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
草地生态学 880
Threaded Harmony: A Sustainable Approach to Fashion 799
Basic Modern Theory of Linear Complex Analytic 𝑞-Difference Equations 510
Queer Politics in Times of New Authoritarianisms: Popular Culture in South Asia 500
Livre et militantisme : La Cité éditeur 1958-1967 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 3059244
求助须知:如何正确求助?哪些是违规求助? 2715321
关于积分的说明 7444545
捐赠科研通 2360696
什么是DOI,文献DOI怎么找? 1250963
科研通“疑难数据库(出版商)”最低求助积分说明 607584
版权声明 596432