ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds |
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Authors: | Osaka Nao Takahashi Takumi Murakami Shiori Matsuzawa Atsushi Noguchi Takuya Fujiwara Takeshi Aburatani Hiroyuki Moriyama Keiji Takeda Kohsuke Ichijo Hidenori |
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Affiliation: | Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan. |
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Abstract: | Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein 3-kinase family that activates both c-Jun NH(2)-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. |
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