Laminin-511, inducer of hair growth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia.
BACKGROUND
Chemotherapy-induced alopecia (CIA) has a devastating cosmetic effect, especially in the young. Recent data indicate that two major basement membrane components (laminin-332 and -511) of the skin have opposing effects on hair growth.


OBJECTIVE
In this study, we examined the role and localization of laminin-332 and -511 in CIA.


METHODS
We examined the expression of laminin-332 and -511 during the dystrophic catagen form of CIA induced in C57BL/6 mice by cyclophosphamide (CYP) treatment.


RESULTS
Our data indicate that both laminin-332 and its receptor alpha 6 beta 4 integrin are up-regulated (both quantitatively and spatially) after mid to late dystrophic catagen around the outer root sheath (ORS) in the lower third of hair follicles in CIA. This up-regulation also occurs at the transcriptional level. In contrast, laminin-511 is down-regulated after mid dystrophic catagen at the protein level, with transcriptional inactivation of laminin-511 occurring transiently at the early dystrophic catagen stage in both epidermal and ORS keratinocytes. Laminin-511 expression correlates with expression of alpha 3 integrin in CIA and we also demonstrate that laminin-511 can up-regulate the activity of the alpha 3 integrin promoter in cultured keratinocytes. Injection of a laminin-511 rich protein extract, but not recombinant laminin-332, in the back skin of mice delays hair loss in CYP-induced CIA.


CONCLUSIONS
We propose that abrupt hair loss in CIA is, at least in part, caused by down-regulation of laminin-511 and up-regulation of laminin-332 at the transcriptional and translational levels.
Imanishi
Hisayoshi
H
Department of Dermatology Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Tsuruta
Daisuke
D
Tateishi
Chiharu
C
Sugawara
Koji
K
Paus
Ralf
R
Tsuji
Tsutomu
T
Ishii
Masamitsu
M
Ikeda
Kazuo
K
Kunimoto
Hiroyuki
H
Nakajima
Koichi
K
Jones
Jonathan C R
JC
Kobayashi
Hiromi
H
D000505:Alopecia / Q000139:chemically induced* / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006197:Hair / Q000254:growth & development; D018859:Hair Follicle / Q000378:metabolism; D007271:Injections, Intradermal; D039422:Integrin alpha3 / Q000378:metabolism; D039663:Integrin beta4 / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D015854:Up-Regulation / Q000502:physiology*; D000097794:Kalinin
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D039422:Integrin alpha3; D039663:Integrin beta4; D007797:Laminin; D000097794:Kalinin; C531281:laminin-511, mouse