June 2004
Versican expression by dermal papilla-regenerated
hair follicles – a promising tool for hair-regrowth products
International Journal of Cosmetic Science June 2004,
Abstract:
Hair follicle stem cells and dermal papilla cells play essential roles in the
cyclical hair regeneration process. However, compared with the recent progress
of follicular stem cell research, detailed analysis of dermal papilla cells is
virtually unknown. We have focused on a large chondroitin sulfate proteoglycan
molecule, versican, and prove its pivotal role in hair follicle induction both
in vitro and in vivo.
First, we examined versican expression with hair cycling
by in situ hybridization (mRNA) and immunohistochemistry (protein). Results
clearly showed specific versican expression in anagen onset of dermal papilla
cells implying a function role of versican in hair induction.
We then generated
transgenic lines with LacZ or green fluorescent protein reporter genes under a
versican regulatory element (promoter) control, and confirmed dermal
papilla-specific activation of the reporter. These transgenic lines were
utilized to isolate the dermal papilla cell population by means of a fluorescent
activated cell sorter.
While freshly isolated dermal papilla cells were able to induce hair growth in a
skin reconstitution assay when grafted with undifferentiated epidermal cells,
this ability and versican expression were rapidly lost during passages in
culture.
In order to examine the functional role of versican in hair growth
induction, versican full-length cDNAs were transfected into inactive passaged
dermal papilla cells. Impressively, this forced expression of versican molecules
partially restored hair inductivity of dermal papilla cells in a skin
reconstitution assay.
These results demonstrated the pivotal role of versican in
hair induction both in vitro and in vivo and will connect the missing link
between the signal from dermal papilla cells to follicular stem cells, and
initiation of hair regeneration.
We have also shown that the hair
growth-promoting compound, cyclosporin A, can upregulate versican expression
implying the application of a novel screening approach for hair growth-promoting
compounds by monitoring versican expression as an indicator.
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