Figure 5.
P2Y2R is required for vascular coordination of liver regeneration. (A) Ki67 staining of hepatocytes is shown at various time points postpartial hepatectomy. At day 2 postpartial hepatectomy, the number of replicating hepatocytes is significantly lower in mice null for P2Y2R compared with wild-type (P = .003). (B) Proliferative responses ([3H]-thymidine) of hepatocytes to combinations of ATP (100 μmol/L) and/or a submitogenic dose of HGF (20 ng/mL) were studied. Synergistic effects of ATP and HGF in the boosting of proliferation of P2Y2R null hepatocytes are attenuated in a statistically significant manner when compared with wild-type hepatocytes. (C) Phosphorylation of VEGFR2 in LSEC was studied following P2Y2R costimulation with VEGF. In mice null for P2Y2R, phospho-VEGFR2 levels do not increase in response to UTP or to low concentrations of VEGF. Phosphorylation of VEGFR2 is substantively attenuated after optimal VEGF and UTP stimulation.(D)Hepatocellular proliferation postpartial hepatectomy in wild-type mice is increased by continuous infusion of apyrase (8.3 U/kg/h) (*P = .027). ATP (0.8 μmol/kg/h) and the A2A agonist ATL146e (600 ng/kg/h) had no significant effects on hepatocyte proliferation. (E) Images of Ki67 staining in wild-type livers postapyrase supplementation. Values are given as mean ± standard error. Levels of significance were assessed by unpaired t tests and ANOVA. P values are as indicated.