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An underlying mechanism of hair loss in acrodermatitis enteropathica
Abstracts from the 41st Annual Meeting / Journal of Dermatological Science 86 (2017) e1–e95
that compartmentalized epidermal stem cells in the upper bulge are involved not only in epidermal maintenance and regeneration, but also in tactile sensation via providing a specialized ECM environment for sensory end organs. http://dx.doi.org/10.1016/j.jdermsci.2017.02.177 P09-07[C07-7] Enhanced survival of hair follicle allografts by anti-ICAM-1 antibody in nonhuman primates Jin Yong Kim 1,2 , Su-Cheol Han 3 , Wooseok Koh 4 , Kyeong Cheon Jung 5 , Kyu Han Kim 1,2 , Ohsang Kwon 1,2,∗ 1 Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea 2 Laboratory of Cutaneous Aging and Hair Research, Seoul National University Hospital, Institute of Human-Environment Interface Biology, Seoul National University, Seoul, South Korea 3 Non-Human Primate Center, Jeonbuk Department, Korea Institute of Toxicology, Jeongeup, South Korea 4 JMO Dermatology, Seoul, South Korea 5 Transplantation Research Institute, Seoul National University College of Medicine, Seoul, South Korea Permanent severe alopecia patients cannot benefit from autologous hair transplantation. However, it would be possible to utilize allogeneic hair follicles (HFs) as the donor source with induction of antigen-specific T cell tolerance. Recently, anti-ICAM-1 antibody (MD-3) was developed to induce dendritic cell arrest in a semi-mature stage and antigen-specific T cell tolerance in situ. In this study, we evaluated the tolerogenic potential of MD-3 under the skin immune system in HF allograft model of nonhuman primates. Following the preparation of recipient sites with a hair removing diode laser, HFs from monkey’s thick eyebrow were transplanted under MD-3 pretreatment and short-term immunosuppressant. The number of visible HF allografts was maintained in MD-3 group, whereas those were rapidly decreased in immunosuppressant and control groups. On histological examination, the outer root sheath of HF allograft was intact over several weeks in MD-3 group, whereas those were rapidly impaired in other groups. MD-3 significantly delayed and diminished perifollicular T cell infiltration. Although long-term survival was not achieved, MD-3 markedly enhanced HF allograft survival regardless of the concomitant immunosuppressant. In conclusion, MD-3 proved to have a therapeutic potential in preventing allograft rejection, and HF allograft model in nonhuman primates is an effective for transplantation research.
http://dx.doi.org/10.1016/j.jdermsci.2017.02.178 P09-08[O3-01] BNIP3 upregulation via stimulation of ERK and JNK activity is required for the protection of keratinocytes from UVB-induced apoptosis Mariko Moriyama ∗ , Takashi Morita, Takao Hayakawa, Hiroyuki Moriyama Pharmaceutical Research and Technology Institute, Kindai University, Osaka, Japan The human skin plays an important role in barrier function. Ultraviolet rays (UV) from sunlight exposure can cause cell apoptosis in the skin epidermis, resulting in the disruption of the barrier. Previously, we have demonstrated that BNIP3 stimulates
e61
autophagy in epidermal keratinocytes and has a protective effect in these cells upon UVB irradiation. In this study, we found that the accumulation of reactive oxygen species (ROS) by UVB irradiation was sufficient to trigger the activation of JNK and ERK mitogen-activated protein kinase (MAPK) in human primary epidermal keratinocytes. In turn, activated JNK and ERK MAPK mediated the upregulation of BNIP3 expression. Treatment with an anti-oxidant reagent or a specific inhibitor of MAPK, U0126, and a JNK inhibitor significantly attenuated the expression of BNIP3 triggered by UVB, followed by the induction of cell death by apoptosis. Furthermore, UVB-induced apoptosis was significantly stimulated by chloroquine or bafilomycin A1, an inhibitor of autophagy. Moreover, BNIP3 was required for the mitochondria degradation upon UVB irradiation. These data clearly indicated that BNIP3-induced autophagy, which occurs via UVB-generated ROSmediated JNK and ERK MAPK activation, plays a crucial role in the protection of the skin epidermis against UVB irradiation. http://dx.doi.org/10.1016/j.jdermsci.2017.02.179 P09-09[O3-02] An underlying mechanism of hair loss in acrodermatitis enteropathica Youichi Ogawa ∗ , Tatsuyoshi Kawamura, Shinji Shimada Department of Dermatology, University of Yamanashi, Yamanashi, Japan The triad of acrodermatitis enteropathica (AE) is dermatitis, diarrhea and hair loss. 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. Dermal papilla (DP) cells of ZD mice were obviously atrophic and lacked the expression of tissue-nonspecific alkaline phosphatase (TNAP), a zinc dependent enzyme, that has been reported to be critical for hair regeneration. 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, PDGF expression was significantly downregulated in ZD dermis compared with ZA dermis. These data suggest that Zn deficiency decreases the production of PDGF 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. http://dx.doi.org/10.1016/j.jdermsci.2017.02.180
that compartmentalized epidermal stem cells in the upper bulge are involved not only in epidermal maintenance and regeneration, but also in tactile sensation via providing a specialized ECM environment for sensory end organs. http://dx.doi.org/10.1016/j.jdermsci.2017.02.177 P09-07[C07-7] Enhanced survival of hair follicle allografts by anti-ICAM-1 antibody in nonhuman primates Jin Yong Kim 1,2 , Su-Cheol Han 3 , Wooseok Koh 4 , Kyeong Cheon Jung 5 , Kyu Han Kim 1,2 , Ohsang Kwon 1,2,∗ 1 Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea 2 Laboratory of Cutaneous Aging and Hair Research, Seoul National University Hospital, Institute of Human-Environment Interface Biology, Seoul National University, Seoul, South Korea 3 Non-Human Primate Center, Jeonbuk Department, Korea Institute of Toxicology, Jeongeup, South Korea 4 JMO Dermatology, Seoul, South Korea 5 Transplantation Research Institute, Seoul National University College of Medicine, Seoul, South Korea Permanent severe alopecia patients cannot benefit from autologous hair transplantation. However, it would be possible to utilize allogeneic hair follicles (HFs) as the donor source with induction of antigen-specific T cell tolerance. Recently, anti-ICAM-1 antibody (MD-3) was developed to induce dendritic cell arrest in a semi-mature stage and antigen-specific T cell tolerance in situ. In this study, we evaluated the tolerogenic potential of MD-3 under the skin immune system in HF allograft model of nonhuman primates. Following the preparation of recipient sites with a hair removing diode laser, HFs from monkey’s thick eyebrow were transplanted under MD-3 pretreatment and short-term immunosuppressant. The number of visible HF allografts was maintained in MD-3 group, whereas those were rapidly decreased in immunosuppressant and control groups. On histological examination, the outer root sheath of HF allograft was intact over several weeks in MD-3 group, whereas those were rapidly impaired in other groups. MD-3 significantly delayed and diminished perifollicular T cell infiltration. Although long-term survival was not achieved, MD-3 markedly enhanced HF allograft survival regardless of the concomitant immunosuppressant. In conclusion, MD-3 proved to have a therapeutic potential in preventing allograft rejection, and HF allograft model in nonhuman primates is an effective for transplantation research.
http://dx.doi.org/10.1016/j.jdermsci.2017.02.178 P09-08[O3-01] BNIP3 upregulation via stimulation of ERK and JNK activity is required for the protection of keratinocytes from UVB-induced apoptosis Mariko Moriyama ∗ , Takashi Morita, Takao Hayakawa, Hiroyuki Moriyama Pharmaceutical Research and Technology Institute, Kindai University, Osaka, Japan The human skin plays an important role in barrier function. Ultraviolet rays (UV) from sunlight exposure can cause cell apoptosis in the skin epidermis, resulting in the disruption of the barrier. Previously, we have demonstrated that BNIP3 stimulates
e61
autophagy in epidermal keratinocytes and has a protective effect in these cells upon UVB irradiation. In this study, we found that the accumulation of reactive oxygen species (ROS) by UVB irradiation was sufficient to trigger the activation of JNK and ERK mitogen-activated protein kinase (MAPK) in human primary epidermal keratinocytes. In turn, activated JNK and ERK MAPK mediated the upregulation of BNIP3 expression. Treatment with an anti-oxidant reagent or a specific inhibitor of MAPK, U0126, and a JNK inhibitor significantly attenuated the expression of BNIP3 triggered by UVB, followed by the induction of cell death by apoptosis. Furthermore, UVB-induced apoptosis was significantly stimulated by chloroquine or bafilomycin A1, an inhibitor of autophagy. Moreover, BNIP3 was required for the mitochondria degradation upon UVB irradiation. These data clearly indicated that BNIP3-induced autophagy, which occurs via UVB-generated ROSmediated JNK and ERK MAPK activation, plays a crucial role in the protection of the skin epidermis against UVB irradiation. http://dx.doi.org/10.1016/j.jdermsci.2017.02.179 P09-09[O3-02] An underlying mechanism of hair loss in acrodermatitis enteropathica Youichi Ogawa ∗ , Tatsuyoshi Kawamura, Shinji Shimada Department of Dermatology, University of Yamanashi, Yamanashi, Japan The triad of acrodermatitis enteropathica (AE) is dermatitis, diarrhea and hair loss. 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. Dermal papilla (DP) cells of ZD mice were obviously atrophic and lacked the expression of tissue-nonspecific alkaline phosphatase (TNAP), a zinc dependent enzyme, that has been reported to be critical for hair regeneration. 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, PDGF expression was significantly downregulated in ZD dermis compared with ZA dermis. These data suggest that Zn deficiency decreases the production of PDGF 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. http://dx.doi.org/10.1016/j.jdermsci.2017.02.180