ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds.
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.
Osaka
Nao
N
Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Takahashi
Takumi
T
Murakami
Shiori
S
Matsuzawa
Atsushi
A
Noguchi
Takuya
T
Fujiwara
Takeshi
T
Aburatani
Hiroyuki
H
Moriyama
Keiji
K
Takeda
Kohsuke
K
Ichijo
Hidenori
H
D000818:Animals; D016026:Bone Marrow Transplantation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D005260:Female; D005819:Genetic Markers / Q000235:genetics / Q000276:immunology; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000254:growth & development / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D005819:Genetic Markers; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse