Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival
| Autor: | Linda Lorenz, Jong-Hee Hwang, Eckhard Lammert, Nicole Eichhorst, Richard Holtmeier, Carina Henning, Harri Nurmi, Tobias Buschmann, Daniel Eberhard, Jennifer Axnick, Kálmán Bódis, Dieter Häussinger, Jörg Stypmann, Shentong Fang, Michael Roden, Oliver Kuss, Sofia Urner, Kari Alitalo, Karsten Müssig |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Endothelium Liver cytology Angiogenesis Biology Mechanotransduction Cellular 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Humans Mechanotransduction Cells Cultured Multidisciplinary Hepatocyte Growth Factor Integrin beta1 Endothelial Cells Middle Aged Vascular Endothelial Growth Factor Receptor-3 Cell biology Mice Inbred C57BL Autocrine Communication 030104 developmental biology medicine.anatomical_structure Liver 030220 oncology & carcinogenesis Hepatocyte Hepatocytes Hepatocyte growth factor Female Bone marrow medicine.drug Blood vessel Signal Transduction |
| Zdroj: | Nature. 562(7725) |
| ISSN: | 1476-4687 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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