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Hypoxia improves hair inductivity of dermal papilla cells via nuclear NADPH oxidase 4‐mediated reactive oxygen species generation'
Author(s) -
Zheng M.,
Jang Y.,
Choi N.,
Kim D. Y.,
Han T.W.,
Yeo J. H.,
Lee J.,
Sung J.H.
Publication year - 2019
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.17706
Subject(s) - nadph oxidase , nox4 , microbiology and biotechnology , hair follicle , reactive oxygen species , hypoxia (environmental) , chemistry , hair loss , dermal papillae , biology , oxygen , organic chemistry , genetics
Summary Background Dermal papilla cells ( DPC s) play a key role in hair regeneration and morphogenesis. Therefore, tremendous efforts have been made to promote DPC hair inductivity. Objectives The aim of this study was to investigate the mitogenic and hair inductive effects of hypoxia on DPC s and examine the underlying mechanism of hypoxia‐induced stimulation of DPC s. Methods DPC s' hair inductivity was examined under normoxia (20% O 2 ) and hypoxia (2% O 2 ). Results Hypoxia significantly increased the proliferation and delayed senescence of DPC s via Akt phosphorylation and downstream pathways. Hypoxia upregulated growth factor secretion of DPC s through the mitogen‐activated protein kinase pathway. Hypoxia‐preconditioned DPC s induced the telogen‐to‐anagen transition in C 3 H mice, and also enhanced hair neogenesis in a hair reconstitution assay. Injected green fluorescent protein‐labelled DPC s migrated to the outer root sheath of the hair follicle, and hypoxia‐preconditioning increased survival and migration of DPC s in vivo . Conditioned medium obtained from hypoxia increased the hair length of mouse vibrissa follicles via upregulation of alkaline phosphatase, vascular endothelial growth factor, and glial cell line‐derived neurotrophic factor. We examined the mechanism of this hypoxia‐induced stimulation, and found that reactive oxygen species ( ROS ) play a key role. For example, inhibition of ROS generation by N ‐acetylcysteine or diphenyleneiodonium treatment attenuated DPC s' hypoxia‐induced stimulation, but treatment with ROS donors induced mitogenic effects and anagen transition. NADPH oxidase 4 is highly expressed in the DPC nuclear region, and NOX 4 knockout by CRISPR ‐Cas9 attenuated the hypoxia‐induced stimulation of DPC s. Conclusions Our results suggest that DPC culture under hypoxia has great advantages over normoxia, and is a novel solution for producing DPC s for cell therapy.Whatʼs already known about this topic?Dermal papilla cells (DPCs) play a key role in hair regeneration and morphogenesis, but they are difficult to isolate and expand for use in cell therapy. Tremendous efforts have been made to increase proliferation of DPCs and promote their hair formation ability.What does this study add?Hypoxia (2% O 2 ) culture of DPCs increases proliferation, delays senescence and enhances hair inductivity of DPCs. Reactive oxygen species play a key role in hypoxia‐induced stimulation of DPC.What is the translational message?Preconditioning DPCs under hypoxia improves their hair regenerative potential, and is a novel solution for producing DPCs for cell therapy to treat hair loss.