Figure 7

Activated platelets recruit VEGFR1⁺ myeloid cells to reinforce angiocrine-mediated liver repair. (a) Recruited VEGFR1⁺ cells in the liver co-expressed CD11b and were associated with VEGFR3⁺ LSECs, as revealed by immunostaining. Scale bar, 50 μm. (b, c) Conditional knockout of Vegfr1 in myeloid cells abrogated hepatocyte proliferation after CCl₄ injection. Floxed Vegfr1 mice were bred with LysM-driven Cre to generate mice lacking Vegfr1 in myeloid cells (Vegfr1^lyzM/lyzM). Quantification of Vegfr1 transcriptional level in myeloid cells is shown in c; N=5 mice per group. (d) Exacerbated liver injury in Vegfr1^lyzM/lyzM mice than WT control, as evidenced by elevated plasma level of alanine aminotransferase, ALT. Injection of thrombopoietin (+TPO) prevented liver parenchymal injury in Vegfr1^lyzM/lyzM mice; N=5–7 mice per group. (e) Pro-regenerative Id1 angiocrine pathway was suppressed in Vegfr1^lyzM/lyzM mice, which was elevated by thrombopoietin injection (+TPO). Compared to WT control mice, transcriptional level of Id1 was lower in Vegfr1^lyzM/lyzM mice after CCl₄ injury. *P<0.05, compared to Vegfr1^lyzM/lyzM group. N=5–7 mice per group. (f) Schema depicting the contribution of hematopoietic–vascular niche for liver regeneration. Upon liver injury, activated platelets are recruited to the liver and produce SDF-1 to activate CXCR7⁺ LSECs, initiating endothelial paracrine/angiocrine-mediated liver repair. Activation of VEGFR1⁺ myeloid cells by platelet VEGF-A further stimulate Id1-Wnt2/HGF angiocrine pathway in LSEC, reinforcing liver regeneration.