Melanocortin/MC5R axis promotes hematopoietic regeneration in irradiated mice. (A,B) Flow cytometric analysis of the expression of (A) p-AKT and (B) p-ERK1/2 in LT-HSCs from the BM of WT mice treated with saline or α-MSH, along with vehicle, AKT inhibitor MK-2206, or ERK1/2 inhibitor PD325901 (n = 6). (C) Cell cycle analysis of LT-HSCs from the BM of WT mice treated with saline or α-MSH along with vehicle, MK-2206, or PD325901 (n = 6). (D,E) The number of (D) MPs, LSKs, and (E) LT-HSCs from the BM of WT mice treated with saline or α-MSH, along with vehicle, MK-2206, or PD325901, 15 days after 5.0 Gy TBI (n = 6). (F-H) The counts of (F) WBC, (G) RBC, and (H) PLT in the PB of WT mice treated with saline or α-MSH, along with vehicle, MK-2206, or PD325901, at the indicated time after 5.0 Gy TBI (n = 10). (I) The survival rates of WT mice treated with saline or α-MSH, along with vehicle, MK-2206, or PD325901, after 7.5 Gy TBI (n = 10). (A-H) One-way ANOVA with Tukey multiple comparisons test; (I) Log-rank test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ^#P < .05; ^##P < .01; †P < .05; ††P < .01. NS, not significant.