血管生成
机械转化
细胞生物学
生物
正弦波
肝细胞生长因子
内皮
骨髓
肝细胞
病理
癌症研究
内分泌学
免疫学
医学
体外
受体
生物化学
作者
Linda F. Lorenz,Jennifer Axnick,Tobias Buschmann,Carina Henning,Sofia Urner,Shentong Fang,Harri Nurmi,Nicole Eichhorst,Richard Holtmeier,Hadi Al‐Hasani,Jonghee Hwang,Karsten Müssig,Daniel Eberhard,Jörg Stypmann,Oliver Kuß,Michael Roden,Kari Alitalo,Dieter Häussinger,Eckhard Lammert
出处
期刊:Nature
[Springer Nature]
日期:2018-09-25
卷期号:562 (7725): 128-132
被引量:130
标识
DOI:10.1038/s41586-018-0522-3
摘要
Angiocrine signals derived from endothelial cells are an important component of intercellular communication and have a key role in organ growth, regeneration and disease1–4. These signals have been identified and studied in multiple organs, including the liver, pancreas, lung, heart, bone, bone marrow, central nervous system, retina and some cancers1–4. Here we use the developing liver as a model organ to study angiocrine signals5,6, and show that the growth rate of the liver correlates both spatially and temporally with blood perfusion to this organ. By manipulating blood flow through the liver vasculature, we demonstrate that vessel perfusion activates β1 integrin and vascular endothelial growth factor receptor 3 (VEGFR3). Notably, both β1 integrin and VEGFR3 are strictly required for normal production of hepatocyte growth factor, survival of hepatocytes and liver growth. Ex vivo perfusion of adult mouse liver and in vitro mechanical stretching of human hepatic endothelial cells illustrate that mechanotransduction alone is sufficient to turn on angiocrine signals. When the endothelial cells are mechanically stretched, angiocrine signals trigger in vitro proliferation and survival of primary human hepatocytes. Our findings uncover a signalling pathway in vascular endothelial cells that translates blood perfusion and mechanotransduction into organ growth and maintenance. In mouse and human liver models, blood vessel perfusion and mechanical stretching release angiocrine signals from endothelial cells that lead to hepatocyte survival and liver growth.
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