Antisense oligonucleotide targeting fibroblast growth factor receptor (FGFR)-1 stimulates cellular activity of hair follicles in an in vitro organ culture system.

Abstract:

BACKGROUND:The hair cycle is regulated by various molecules, among which FGF-5 has been shown to promote the transition from anagen to catagen. The FGFR-1, a trans-membrane receptor of FGF-5 with tyrosine kinase activity, is localized in the follicular papilla of hair follicles. OBJECTIVES:In order to apply the antisense oligonucleotides targeting FGFR-1 as a treatment for baldness, we examined the effect of the oligonucleotides on hair follicle growth in a serum-free organ culture system. METHODS:Vibrissal hair follicles from C3H/He mice were cultured in the presence of a reagent at 31 degrees C in 95% O(2)-5% CO(2) for 72 h. A 20-mer antisense nucleotide and its randomly arranged counterpart were prepared by predicting the effective target site of FGFR-1 mRNA. Cellular activity in the hair bulb was estimated by measuring the fluorescence intensity (FI) of the medium after incubation with AlamarBlue dye. RESULTS:The addition of 30 microM of the phosphorothioate form of antisense oligonucleotide (A1561TS) to the media increased the FI by 30%, whereas the control produced no detectable change. This effect was reproducible dose-dependent with maximal stimulation at 30 microM. Incorporation of the oligonucleotide into the follicular papilla was histologically confirmed by incubation with FITC-labeled phosphorothioate oligonucleotides, and the intact morphological structure of the hair bulb was maintained intact after a 72-h incubation. CONCLUSIONS:These results suggest the clinical utility of antisense nucleotide targeting FGFR-1 as a treatment for baldness.

journal_name

Int J Dermatol

authors

Tsuboi R,Yamazaki M,Matsuda Y,Uchida K,Ueki R,Ogawa H

doi

10.1111/j.1365-4632.2007.03018.x

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

259-63

issue

3

eissn

0011-9059

issn

1365-4632

pii

IJD3018

journal_volume

46

pub_type

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