Laminin-511, inducer of hair growth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia

作者：Imanishi Hisayoshi; Tsuruta Daisuke^*; Tateishi Chiharu; Sugawara Koji; Paus Ralf; Tsuji Tsutomu; Ishii Masamitsu; Ikeda Kazuo; Kunimoto Hiroyuki; Nakajima Koichi; Jones Jonathan C R; Kobayashi Hiromi

来源：Journal of Dermatological Science, 2010, 58(1): 43-54.

DOI：10.1016/j.jdermsci.2010.02.005

• A549 cells
• Chemotherapy
• Extracellular matrix
• Hemidesmosome
• Integrin
• Outer root sheath cells

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 (GYP) 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.

• 出版日期2010-4
• 单位西北大学