The Role of gp91phox and the Effect of Tranexamic Acid Administration on Hair Color in Mice.

We observed that on long-term breeding, gp91phox-knockout (gp91phox) mice developed white hair. Here, we investigate the origin of this hitherto unexplained phenomenon. Moreover, we investigated the effect of tranexamic acid administration on the hair color in gp91phox mice. We administered tranexamic acid (about 12 mg/kg/day) orally to 9-week-old C57BL/6j (control) and gp91phox mice, thrice a week for 12 months. Compared to control mice, gp91phox mice showed more white hair. However, the concentrations of reactive oxygen species and the levels of interleukin (IL)-1β and transforming growth factor (TGF)-β in the skin were lower than those in the control group. Furthermore, increase in white hair was observed in the control mice upon administration of the IL-1β antagonist. On the other hand, administration of tranexamic acid led to brown colored hair on gp91phox mice. Although tranexamic acid treatment did not alter the expression levels of melanocortin receptor 1 and agouti signaling protein on hair follicles, it increased the expression of mahogunin ring finger protein 1 (MGRN1) and collagen XVII. These results suggested that retention of black hair requires the gp91phox/ROS/IL-1β/TGF-β pathway and that elevated levels of MGRN1 and collagen XVII lead to brown hair in gp91phox mice.