194 An underlying mechanism of hair loss in acrodermatitis enteropathica

Abstract

The triad of acrodermatitis enteropathica (AE) is dermatitis, diarrhea and hair loss. We previously elucidated an underlying mechanism of characteristic dermatitis in AE using skin samples of AE patients and dietary Zinc (Zn)-deficient mice. We herein assessed underlying mechanisms of hair loss in AE using dietary Zn-adequate (ZA) and -deficient (ZD) mice. Five-week-old female Balb/c mice were continued ZA diet or switched to ZD diet for ZA or ZD mice, respectively. Although ZD mice did not exhibit obvious hair loss, the hair coat of ZD mice was sparse when compared to that of ZA mice. Hair morphology of ZD mice was stuck in telogen stage even after one week and thereafter of initiation of ZD diet, implying disruption of hair cycle. Moreover, depilation of telogen hair of ZA mice induced anagen hair, but not of ZD mice, in which hair did not regrow after depilation. Strikingly, loss of hair cycle and depilation-induced anagen initiation in ZD mice was completely restored by supplementation of Zn to ZD mice, suggesting that functions of some molecules related to hair cycle and regeneration was reversibly impaired by Zn deficiency. Immunofluorescence study revealed that lack of positivity of tissue-nonspecific alkaline phosphatase (TNAP) in dermal papilla (DP) and of P-cadherin in hair germ cells in ZD mice. TNAP, a zinc dependent enzyme, has been reported to be critical for hair regeneration by DP cells. Thus, the lack of TNAP activity in DP cells due to Zn deficiency appeared to be the major cause of loss of hair cycle and depilation-induced anagen initiation in ZD mice. Additionally, qPCR with dermis from ZA and ZD mice revealed downregulation of mRNA expression of pdgfα, pdgfβ, fgf7 and fgf10. These data suggest that Zn deficiency decreases the production of PDGF and FGF in dermal cells including intra-dermal adipocytes, followed by downregulation of TNAP activity in DP cells, thereby resulting in loss of hair cycle and depilation-induced anagen initiation.