Figure 4
Figure 4. Effect of FG-4497 on stabilization of Hif-1α and Hif-2α and the levels of Epo mRNA in the kidney and liver of P4h-tm null, Hif-p4h-2 hypomorphic, and Hif-p4h-3 null mice. The P4h-tm−/− (A), Hif-p4h-2gt/gt (B), and Hif-p4h-3−/− (C) mice and wild-type mice received 3 oral doses of FG-4497 (100 mg/kg) per week for 3 to 5 weeks and were killed 6 hours after the last dose. Anti–Hif-1α and Hif-2α Western blots are shown at 5 weeks in panels A and C and at 3 weeks in panel B (the Hif-p4h-2gt/gt mice were treated only for 3 weeks). The vertical black lines indicate repositioning of lanes from the same or separate gels of the same experiment with the same exposure. The horizontal black line indicates exact rejoining of the lanes of a blot that was originally cut in 2 halves. ns indicates nonspecific. In the case of Epo mRNA values statistical significance is shown only for comparisons between the FG-4497–treated gene-modified and wild-type mice, the means of the latter being taken as 100% (*P < .05, **P < .01, and ***P = .001 in panel B, and < .0001 in panel C). The differences in the kidney and liver Epo mRNA values between the FG-4497–treated and vehicle-treated mice are highly significant, whereas there are no significant differences between the values for the vehicle-treated gene-modified and wild-type mice. Values of n as in Figure 3. Error bars represent SEM.

Effect of FG-4497 on stabilization of Hif-1α and Hif-2α and the levels of Epo mRNA in the kidney and liver of P4h-tm null, Hif-p4h-2 hypomorphic, and Hif-p4h-3 null mice. The P4h-tm−/− (A), Hif-p4h-2gt/gt (B), and Hif-p4h-3−/− (C) mice and wild-type mice received 3 oral doses of FG-4497 (100 mg/kg) per week for 3 to 5 weeks and were killed 6 hours after the last dose. Anti–Hif-1α and Hif-2α Western blots are shown at 5 weeks in panels A and C and at 3 weeks in panel B (the Hif-p4h-2gt/gt mice were treated only for 3 weeks). The vertical black lines indicate repositioning of lanes from the same or separate gels of the same experiment with the same exposure. The horizontal black line indicates exact rejoining of the lanes of a blot that was originally cut in 2 halves. ns indicates nonspecific. In the case of Epo mRNA values statistical significance is shown only for comparisons between the FG-4497–treated gene-modified and wild-type mice, the means of the latter being taken as 100% (*P < .05, **P < .01, and ***P = .001 in panel B, and < .0001 in panel C). The differences in the kidney and liver Epo mRNA values between the FG-4497–treated and vehicle-treated mice are highly significant, whereas there are no significant differences between the values for the vehicle-treated gene-modified and wild-type mice. Values of n as in Figure 3. Error bars represent SEM.

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