Editors' ChoiceINJURY

ASKing Macrophages to Promote Hair Growth

See allHide authors and affiliations

Science's STKE  03 Apr 2007:
Vol. 2007, Issue 380, pp. tw116
DOI: 10.1126/stke.3802007tw116

Noting that the abundance of ASK1 (apoptosis signal-regulating kinase 1, which is activated in response to inflammatory cytokines and various stresses) increases after epithelial injury in rats, Osaka et al. investigated its involvement in the increase in regional hair growth stimulated by skin injury in mice. Wounds in mice lacking ASK1 (ASK1–/– mice) showed apparently normal re-epithelialization, but there was a marked delay in injury-induced hair regrowth. In contrast, hair follicle development in embryos and regrowth after plucking appeared normal. ASK1 is a mitogen-activated protein kinase kinase kinase (MAPKKK), and activation of its downstream targets c-Jun N-terminal kinase and p38 was reduced in ASK1–/– compared with wild-type mice, as was activation of extracellular signal-regulated kinase (the latter likely through an indirect route). A combination of microarray analysis and reverse transcription polymerase chain reaction (RT-PCR) indicated that the expression of macrophage-specific markers, as well as that of macrophage-specific chemotactic and activating factors, was reduced in the wounded skin of ASK1–/– animals compared with that in wild-type mice. Immunohistochemical analysis confirmed that ASK1–/– mice exhibited decreased recruitment of macrophages to the wounded area. Intracutaneous transplantation of bone marrow-derived macrophages (BMDMs) from either wild-type or ASK1–/– mice stimulated notable hair growth only in wild-type mice; intracutaneous transplantation of cytokine-activated BMDMs, however, stimulated marked hair growth in both wild-type and ASK1–/– mice. Thus, ASK1-dependent recruitment and activation of macrophages appears to play a critical role in promoting hair growth after injury.

N. Osaka, T. Takahashi, S. Murakami, A. Matsuzawa, T. Noguchi, T. Fujiwara, H. Aburatani, K. Moriyama, K. Takeda, H. Ichijo, ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds. J. Cell Biol. 176, 903-909 (2007). [Abstract] [Full Text]

Stay Connected to Science Signaling