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Platelets prime hematopoietic–vascular niche to drive angiocrine-mediated liver regeneration
In mammals, the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy. How liver regeneration is initiated after mass loss remains to be defined. Here we report that following liver injury, activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7(+) liver sinusoid...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661617/ https://www.ncbi.nlm.nih.gov/pubmed/29201496 http://dx.doi.org/10.1038/sigtrans.2016.44 |
Sumario: | In mammals, the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy. How liver regeneration is initiated after mass loss remains to be defined. Here we report that following liver injury, activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7(+) liver sinusoidal endothelial cell (LSEC) and VEGFR1(+) myeloid cell, orchestrating hepatic regeneration. After carbon tetrachloride injection or hepatectomy, platelets and CD11b(+)VEGFR1(+) myeloid cells were recruited to LSECs, and liver regeneration in both models was impaired in thrombopoietin-deficient (Thpo(−/−)) mice repressing production of circulating platelets. This impeded regeneration phenotype was recapitulated in mice with either conditional ablation of Cxcr7 in LSEC (Cxcr7(iΔ/iΔ)) or Vegfr1 in myeloid cell (Vegfr1(lysM/lysM)). Both Vegfr1(lysM/lysM) and Cxcr7(iΔ/iΔ) mice exhibited suppressed expression of hepatocyte growth factor and Wnt2, two crucial trophogenic angiocrine factors instigating hepatocyte propagation. Of note, administration of recombinant thrombopoietin restored the prohibited liver regeneration in the tested genetic models. As such, our data suggest that platelets and myeloid cells jointly activate the vascular niche to produce pro-regenerative endothelial paracrine/angiocrine factors. Modulating this ‘hematopoietic–vascular niche’ might help to develop regenerative therapy strategy for hepatic disorders. |
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