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J. Cell Biol. 176 (7): 903-909

Copyright © 2007 by the Rockefeller University Press.

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ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds

Nao Osaka1,2,3, Takumi Takahashi4, Shiori Murakami1,2,3, Atsushi Matsuzawa1,2,3, Takuya Noguchi1,2,3, Takeshi Fujiwara3, Hiroyuki Aburatani5, Keiji Moriyama4, Kohsuke Takeda1,2,3, , and Hidenori Ichijo1,2,3

1 Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 2 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, and 3 Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, Center of Excellence Program, Bunkyo-ku, Tokyo 113-0033, Japan
4 Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan
5 Genome Science Division, Research Center for Advanced Science and Technology and Department, The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan

Correspondence to Hidenori Ichijo: ichijo{at}mol.f.u-tokyo.ac.jp

Abstract: Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein 3-kinase family that activates both c-Jun NH2-terminal kinase and p38 pathways in response to inflammatory cytokines and physicochemical stress. We report that ASK1 deficiency in mice results in dramatic retardation of wounding-induced hair regrowth in skin. Oligonucleotide microarray analysis revealed that expression of several chemotactic and activating factors for macrophages, as well as several macrophage-specific marker genes, was reduced in the skin wound area of ASK1-deficient mice. Intracutaneous transplantation of cytokine-activated bone marrow-derived macrophages strongly induced hair growth in both wild-type and ASK1-deficient mice. These findings indicate that ASK1 is required for wounding-induced infiltration and activation of macrophages, which play central roles in inflammation-dependent hair regrowth in skin.

Abbreviations used in this paper: ASK1, apoptosis signal-regulating kinase 1; BMDM, bone marrow–derived macrophage; DC, dendritic cell; ERK, extracellular signal-regulated kinase; IL, interleukin; MCP-1, monocyte chemoattractant protein-1; MEF, mouse embryonic fibroblast; MHC, major histocompatability complex; MIP-1{alpha}, macrophage inflammatory protein-1{alpha}; MSP, macrophage-stimulating factor; WT, wild-type.

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ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds.
N. Osaka, T. Takahashi, S. Murakami, A. Matsuzawa, T. Noguchi, T. Fujiwara, H. Aburatani, K. Moriyama, K. Takeda, and H. Ichijo (2007)
J. Exp. Med. 204, i9
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