lncRNA Helf promotes hepatic inflammation and fibrosis by interacting with PTBP1 to facilitate PIK3R5 mRNA stabilization

肝星状细胞 肝纤维化 炎症 纤维化 基因沉默 癌症研究 蛋白激酶B 生物 细胞生物学 体内 信号转导 免疫学 医学 内科学 基因 内分泌学 生物化学 生物技术
作者
Xiaohui Han,Beichen Guo,Sicong Zhao,Yehua Li,Jun Zhu,Yaqin He,Jiajun Wang,Qingbin Yao,Shuai Shao,Lemin Zheng,Zhemin Shi,Tao Han,Hong Wang,Kun Zhang
出处
期刊:Cellular & Molecular Biology Letters [Springer Nature]
卷期号:28 (1)
标识
DOI:10.1186/s11658-023-00492-3
摘要

Abstract Background Hepatic fibrosis is a common consequence of chronic liver diseases without approved antifibrotic therapies. Long noncoding RNAs (lncRNAs) play an important role in various pathophysiological processes. However, the functions of certain lncRNAs involved in mediating the antifibrotic role remain largely unclear. Methods The RNA level of lnc-High Expressed in Liver Fibrosis (Helf) was detected in both mouse and human fibrotic livers. Furthermore, lnc-Helf-silenced mice were treated with carbon tetrachloride (CCl 4 ) or bile duct ligation (BDL) to investigate the function of lnc-Helf in liver fibrosis. Results We found that lnc-Helf has significantly higher expression in human and mouse fibrotic livers as well as M1 polarized hepatic macrophages (HMs) and activated hepatic stellate cells (HSCs). In vivo studies showed that silencing lnc-Helf by AAV8 vector alleviates CCl 4 - and BDL-induced hepatic inflammation and fibrosis. Furthermore, in vitro experiments revealed that lnc-Helf promotes HSCs activation and proliferation, as well as HMs M1 polarization and proliferation in the absence or presence of cytokine stimulation. Mechanistically, our data illustrated that lnc-Helf interacts with RNA binding protein PTBP1 to promote its interaction with PIK3R5 mRNA, resulting in increased stability and activating the AKT pathway, thus promoting HSCs and HMs activation and proliferation, which augments hepatic inflammation and fibrosis. Conclusion Our results unveil a lnc-Helf/PTBP1/PIK3R5/AKT feedforward, amplifying signaling that exacerbates the process of hepatic inflammation and fibrosis, thus providing a possible therapeutic strategy for hepatic fibrosis.
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
顾矜应助牙牙采纳,获得10
1秒前
Bey发布了新的文献求助10
2秒前
可靠的寻云完成签到,获得积分10
3秒前
小沐完成签到,获得积分10
5秒前
7秒前
研友_VZG7GZ应助源妮儿儿采纳,获得10
11秒前
Yolenders发布了新的文献求助10
11秒前
HCLonely应助卓涵柏采纳,获得10
11秒前
11秒前
12秒前
杳鸢应助我不想秃采纳,获得10
12秒前
12秒前
Hello应助大侦探皮卡丘采纳,获得10
13秒前
君山露友完成签到 ,获得积分10
14秒前
15秒前
无花果应助大大大飞机采纳,获得10
15秒前
yht18893912614完成签到,获得积分20
15秒前
帅气的Q应助gu采纳,获得10
15秒前
whtestar完成签到,获得积分10
15秒前
16秒前
KYJR发布了新的文献求助10
17秒前
魏魏关注了科研通微信公众号
17秒前
20秒前
20秒前
20秒前
21秒前
zouwenting发布了新的文献求助10
21秒前
glowworm完成签到 ,获得积分10
23秒前
sky完成签到 ,获得积分10
24秒前
24秒前
jbz发布了新的文献求助10
25秒前
bukeshuo发布了新的文献求助10
25秒前
源妮儿儿发布了新的文献求助10
25秒前
Bey完成签到 ,获得积分10
25秒前
隐形曼青应助zq1992nl采纳,获得10
27秒前
27秒前
27秒前
28秒前
31秒前
WWXWWX发布了新的文献求助10
31秒前
高分求助中
Earth System Geophysics 1000
Studies on the inheritance of some characters in rice Oryza sativa L 600
Medicina di laboratorio. Logica e patologia clinica 600
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
Language injustice and social equity in EMI policies in China 500
mTOR signalling in RPGR-associated Retinitis Pigmentosa 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 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 3206716
求助须知:如何正确求助?哪些是违规求助? 2856187
关于积分的说明 8102850
捐赠科研通 2521284
什么是DOI,文献DOI怎么找? 1354291
科研通“疑难数据库(出版商)”最低求助积分说明 641992
邀请新用户注册赠送积分活动 613207