Small cutaneous wounds induce telogen to anagen transition of murine hair follicle stem cells.
BACKGROUND
Recent studies suggest that large (>1 cm) diameter circular cutaneous wounds induce follicular neogenesis in mice. However, the effects of non-circular wounds or smaller circular wounds on the hair follicle cycle remain poorly understood.


OBJECTIVE
We investigated whether non-circular wounds or smaller (≤1 cm) circular wounds could induce early entry of hair follicle stem cells into anagen.


METHODS
We created different shaped and sized full-thickness incisional wounds on the dorsal skin of 6-wk old mice (BALB/c, C57BL/6, and CD1), and then assessed for hair growth, wound contraction rates, and growth factor and/or immunomodulatory cytokine involvement.


RESULTS
By day 16 and through day 26 post-wounding, we observed hair growth in the skin around the wound, but not in distant unwounded skin of BALB/c and C57BL/6 mice. In contrast, CD1 mice showed hair growth in both the wounded and unwounded skin. In all mice, the hair growth pattern was independent of wound type. The area of hair growth induced by a 2 cm linear wound was roughly 2-fold that induced by a 1 cm linear wound and 4-fold that of a 0.5 cm linear wound. Increased γ-glutamyl transpeptidase activity was observed in hair follicles growing in the wounded area as well as an up to 8-fold upregulation of Wnt- and Shh-dependent signaling, consistent with anagen growth.


CONCLUSIONS
Our data strongly support that small cutaneous wounds induce telogen to anagen transition of murine hair follicle stem cells.
Department of Surgery, Stanford University School of Medicine, CA 94305, United States.
Shu
S
Jiang
Longmei
L
Zhao
Takele
T
Teklemariam
Basil M
BM
Hantash
D053687:Adult Stem Cells / Q000473:pathology*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D006197:Hair / Q000254:growth & development; D018859:Hair Follicle / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000293:injuries* / Q000473:pathology* / Q000503:physiopathology; D000073940:Transcription Factor 4; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D053823:Hedgehog Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D012333:RNA, Messenger; D000073940:Transcription Factor 4; D051153:Wnt Proteins; D051176:beta Catenin; D005723:gamma-Glutamyltransferase; C495267:CTNNB1 protein, mouse; C497574:Lef1 protein, mouse; C465570:Shh protein, mouse; C075668:Tcf3 protein, mouse; C090743:Tcf4 protein, mouse