Semaphorin 3C exacerbates liver fibrosis

信号灯 肝星状细胞 纤维化 肌成纤维细胞 肝硬化 生物 癌症研究 免疫学 受体 医学 病理 内科学 内分泌学 遗传学
作者
Francesca Rigotti,Lena Wiedmann,Max Ole Hubert,Margherita Vacca,Sana S. Hasan,Iris Moll,Silvia Carvajal,Wladimiro Jiménez,Maja Starostecka,Adrian T. Billeter,Beat P. Müller‐Stich,Gretchen Wolff,Bilgen Ekim Üstünel,Stephan Herzig,Carolin Mogler,Andreas Fischer,Juan Rodríguez‐Vita
标识
DOI:10.1101/2021.07.29.454292
摘要

Abstract Background & Aims Chronic liver disease is a growing epidemic leading to fibrosis and cirrhosis. TGF-β is the pivotal pro-fibrogenic cytokine which activates hepatic stellate cells (HSC), yet, other molecules can substantially modulate TGF-β signaling in the course of liver fibrosis. Expression of the axon guidance molecules Semaphorins (SEMAs), which signal through Plexins and Neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs. Approach & Results We analyzed publicly available patient databases and liver biopsies. We employed transgenic mice where genes are deleted only in activated HSCs to perform ex vivo analysis and animal models. SEMA3C is the most enriched member of the Semaphorin family in liver samples from cirrhotic patients. Higher expression of SEMA3C in patients with NASH, alcoholic hepatitis or HBV-induced hepatitis discriminates those with a more pro-fibrotic transcriptomic profile. SEMA3C expression is also elevated in different mouse models of liver fibrosis and in isolated HSCs upon activation. In keeping with this, deletion of SEMA3C in activated HSCs reduces myofibroblast marker expression. Conversely, SEMA3C overexpression exacerbates TGF-β-mediated myofibroblast activation, as shown by increased SMAD2 phosphorylation and target gene expression. Among SEMA3C receptors, only NRP2 expression is maintained upon activation of isolated HSCs. Interestingly, lack of NRP2 in those cells reduces myofibroblast marker expression. Finally, deletion of either SEMA3C or NRP2, specifically in activated HSCs, reduces liver fibrosis in mice. Conclusion SEMA3C is a novel marker for activated HSCs that plays a fundamental role in the acquisition of the myofibroblastic phenotype and liver 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
刚刚
吴子行发布了新的文献求助10
1秒前
suli关注了科研通微信公众号
2秒前
秋秋发布了新的文献求助10
2秒前
4秒前
半个芝士发布了新的文献求助80
4秒前
5秒前
elooo发布了新的文献求助10
5秒前
Bae发布了新的文献求助10
5秒前
李健应助邱小七采纳,获得10
5秒前
CipherSage应助吴子行采纳,获得10
6秒前
LUMEN完成签到,获得积分10
6秒前
8秒前
秋秋完成签到,获得积分10
8秒前
9秒前
传统的纸飞机完成签到 ,获得积分10
9秒前
七七完成签到,获得积分20
10秒前
10秒前
831143完成签到 ,获得积分0
11秒前
11秒前
鳗鱼三毒发布了新的文献求助10
13秒前
半个芝士完成签到,获得积分10
14秒前
song发布了新的文献求助10
15秒前
15秒前
永远少年完成签到,获得积分10
16秒前
ckl完成签到,获得积分10
16秒前
JamesPei应助tusyuki采纳,获得10
16秒前
我是老大应助changl2023采纳,获得10
18秒前
无花果应助甘楽采纳,获得10
19秒前
19秒前
CC发布了新的文献求助10
19秒前
憧憬乐发布了新的文献求助10
20秒前
xjcy应助zc采纳,获得10
22秒前
星川发布了新的文献求助10
24秒前
25秒前
Bae完成签到,获得积分20
25秒前
26秒前
烟花应助weifeng采纳,获得10
27秒前
28秒前
30秒前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Microlepidoptera Palaearctica, Volumes 1 and 3 - 13 (12-Volume Set) [German] 1122
The Data Economy: Tools and Applications 1000
Diamonds: Properties, Synthesis and Applications 800
PraxisRatgeber Mantiden., faszinierende Lauerjäger. – Buch gebraucht kaufen 700
Mantiden - Faszinierende Lauerjäger – Buch gebraucht kaufen 700
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 3097793
求助须知:如何正确求助?哪些是违规求助? 2749704
关于积分的说明 7605682
捐赠科研通 2401576
什么是DOI,文献DOI怎么找? 1274203
科研通“疑难数据库(出版商)”最低求助积分说明 616015
版权声明 599016