自分泌GDF10通过BMPR2/ALK3受体抑制肝星状细胞活化预防肝纤维化

IF 14.1 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yinliang Zhang, Xiaochen Gai, Yuhui Li, Zuoyu Chen, Xi Zhang, Wei Qiao, Ping Qiu, Chunyuan Du, Sufang Sheng, Jingran Hao, Yujie Zhang, Heng Fan, Xiaorong Li, Ming Liu, Jun Zhang, Zhe Pan, Yongsheng Chang
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引用次数: 0

摘要

肝星状细胞(HSCs)在肝纤维化的发展中起着核心作用,它们的激活受肝脏微环境中自分泌/旁分泌信号的复杂相互作用控制。在这里,我们发现生长分化因子10 (GDF10)在小鼠和人类肝脏中都是由hsc特异性表达的,并且在激活的hsc中其表达减少。GDF10功能丧失可促进小鼠HSC活化并加重肝纤维化,而GDF10功能的获得可缓解这一病理状况。机制上,自分泌GDF10与BMPR2/ALK3受体结合,在造血干细胞中引发SMAD1/5/8-SMAD7信号通路。激活SMAD1/5/8-SMAD7信号通路抑制TGF-β-SMAD2/3信号转导,这是HSC激活所必需的。此外,重组GDF10蛋白处理可抑制小鼠HSC活化,减轻肝纤维化。综上所述,GDF10是一种抑制HSC活化的自分泌因子,是治疗肝纤维化的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis

Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis

Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis

Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis

Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis, and their activation is controlled by a complex interplay of autocrine/paracrine signals within the liver microenvironment. Here, we show that growth differentiation factor 10 (GDF10) is specifically expressed by HSCs in both mouse and human livers, and its expression is reduced in activated HSCs. Loss of GDF10 function promotes HSC activation and exacerbates liver fibrosis in mice, while gain of GDF10 function alleviates this pathological condition. Mechanistically, autocrine GDF10 binds to BMPR2/ALK3 receptor to elicit SMAD1/5/8-SMAD7 signaling pathway in HSCs. Activated SMAD1/5/8-SMAD7 signaling pathway then inhibits the TGF-β-SMAD2/3 signaling transduction, which is essential for HSC activation. Moreover, recombinant GDF10 protein treatment suppresses HSC activation and alleviates liver fibrosis in mice. In conclusion, GDF10 is an autocrine suppressor of HSC activation and a potential therapeutic target for the treatment of liver fibrosis.

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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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