Expression and function of glycogen synthase kinase-3 in human hair follicles.
Beta-catenin is involved in the hair follicle morphogenesis and stem cell differentiation, and inhibition of glycogen synthase kinase-3 (GSK-3) increases beta-catenin concentration in the cytoplasm. To examine the effects of GSK-3 inhibition on the hair follicle epithelium, we first examined the expression of GSK-3 in plucked human hair follicles by RT-PCR and found GSK-3 expression in hair follicles. Western blotting with a GSK-3beta-specific antibody, Y174, also demonstrated GSK-3beta expression in the follicles. Moreover, GSK-3beta immunostaining with Y174 showed that GSK-3beta colocalized with hair follicle bulge markers. Contrary to GSK-3beta, GSK-3 alpha was widely expressed throughout the follicles when immunostained with a specific antibody, EP793Y. We then investigated the influence of GSK-3 inhibition. A GSK-3 inhibitor, BIO, promoted the growth of human outer root sheath cells, which could be cultured for up to four passages. The BIO-treated cells exhibited smaller and more undifferentiated morphology than control cells. Moreover, in organ culture of plucked human hair, outer root sheath cells in the middle of a hair follicle proliferated when cultured with BIO. These results indicate that GSK-3beta is expressed in hair bulge stem cells and BIO promotes the growth of ORS cells, possibly by regulating the GSK-3 signaling pathway.
Yamauchi
Koichi
K
Hair Clinic Reve-21 Corporation, 2-1-61 Shiromi, Chuo-ku, Osaka, 540-6122, Japan.
Kurosaka
Akira
A
D053687:Adult Stem Cells / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018859:Hair Follicle / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D053569:Keratin-15 / Q000276:immunology / Q000378:metabolism; D053539:Keratin-19 / Q000276:immunology / Q000378:metabolism; D009924:Organ Culture Techniques; D009928:Organ Specificity; D010091:Oximes / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C483321:6-bromoindirubin-3'-oxime; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D007211:Indoles; D053569:Keratin-15; D053539:Keratin-19; D010091:Oximes; D020033:Protein Isoforms; D051176:beta Catenin; D038362:Glycogen Synthase Kinase 3; C042739:antigens, CD200