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Fig. 4 Phenotypic signature and contribution of LSECs to physiological liver regeneration
induced by 70 % partial hepatectomy. a Liver sections obtained from VEGFR2-GFP reporter
mice. During liver regeneration VEGFR2 is exclusively expressed on the liver endothelial cells.
b Restricted expression of VEGFR3 on LSECs, but not CD34 + large vessels or hepatocytes. Scale
bars, 50 lm (Adapted from [ 65 ])
Table
2
Signatures of various cell types in adult liver mice
Cell Type
Markers
VEGFR3 + CD34 2 VEGFR2 + VE-cadherin + FactorVIII + Prox-1 - CD45 -
Liver-sinusoidal ECs
VEGFR3 2 CD34 + VEGFR2 + VE-cadherin +
CD45 -
Non-sinusoidal ECs
VEGFR3 + CD34 + Prox- 1 + FactorVIII - CD45 -
Lymphatic ECs
These results suggest a two-step contribution of LSECs in mediating hepatic
reconstitution. At the early phases of PH (days 1-3 after partial hepatectomy),
inductive angiogenesis in the non-proliferative LSECs stimulates hepatic regen-
eration, possibly by releasing angiocrine factors. In contrast, 4 days after partial
hepatectomy, the increased demand of blood supply for the regenerating liver is
met by proliferative angiogenesis of LSECs.
To investigate the significance of VEGF receptors during liver SEC driven
hepatic regeneration, the VEGFR2 gene was conditionally deleted by crossing
VEGFR2 loxP/loxP mice with ROSA-CreER T2 mice, generating inducible VEGFR2-
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