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 language | English |
|---|---|
| Journal | Journal of Dermatological Science |
| Volume | 58 |
| Issue number | 1 |
| Pages (from-to) | 43-54 |
| Number of pages | 12 |
| ISSN | 0923-1811 |
| DOIs | |
| Publication status | Published - 01.04.2010 |
Funding
We thank Drs. Jeffrey Miner, Peter Marinkovich, and Mike DiPersio for generous gifts of antibody. This work is supported by The 21st Century COE Program “Base to Overcome Fatigue” (2004–2009) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and the Japanese Society for Promoting Science (JSPS) (Grant number does not exist) and The Osaka Medical Research Foundation for Incurable Disease (Grant number is 14-2-2 ). Jonathan Jones is supported by the NIH ( RO1 AR054184 ).
