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

Hisayoshi Imanishi, Daisuke Tsuruta, Chiharu Tateishi, Koji Sugawara, Ralf Paus, Tsutomu Tsuji, Masamitsu Ishii, Kazuo Ikeda, Hiroyuki Kunimoto, Koichi Nakajima, Jonathan C.R. Jones, Hiromi Kobayashi

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10 Scopus citations

Abstract

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 α6β4 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 α3 integrin in CIA and we also demonstrate that laminin-511 can up-regulate the activity of the α3 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.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalJournal of Dermatological Science
Volume58
Issue number1
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Imanishi, H., Tsuruta, D., Tateishi, C., Sugawara, K., Paus, R., Tsuji, T., Ishii, M., Ikeda, K., Kunimoto, H., Nakajima, K., Jones, J. C. R., & Kobayashi, H. (2010). Laminin-511, inducer of hair growth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia. Journal of Dermatological Science, 58(1), 43-54. https://doi.org/10.1016/j.jdermsci.2010.02.005