Expression and function of glycogen synthase kinase-3 in human hair follicles

• Published in: Archives of Dermatological Research Vol. 302; no. 4; pp. 263 - 270
• Main Authors: Yamauchi, Koichi, Kurosaka, Akira
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2010; Springer; Springer Nature B.V
• Subjects: Adult Stem Cells - metabolism; Antibodies, Monoclonal - metabolism; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation - immunology; Antigens, Differentiation - metabolism; beta Catenin - genetics; beta Catenin - metabolism; Biological and medical sciences; Cell Proliferation - drug effects; Cells, Cultured; Dermatology; Gene Expression Regulation, Enzymologic - drug effects; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - immunology; Glycogen Synthase Kinase 3 - metabolism; Hair Follicle - drug effects; Hair Follicle - enzymology; Hair Follicle - immunology; Hair Follicle - pathology; Humans; Indoles - pharmacology; Keratin-15 - immunology; Keratin-15 - metabolism; Keratin-19 - immunology; Keratin-19 - metabolism; Medical sciences; Medicine; Medicine & Public Health; Organ Culture Techniques; Organ Specificity; Original Paper; Oximes - pharmacology; Protein Isoforms - genetics; Protein Isoforms - immunology; Protein Isoforms - metabolism; Signal Transduction; Plucked hair; Transit amplifying cell; Glycogen synthase kinase-3β; Bulge area; Glycogen synthase kinase-3 inhibitor; Outer root sheath; Human; Hair; Enzyme; Dermatology; Glycogen; Transferases; Hair follicle; Hair (head); Kinase
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s00403-009-0987-x

β-Catenin is involved in the hair follicle morphogenesis and stem cell differentiation, and inhibition of glycogen synthase kinase-3 (GSK-3) increases β-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-3β-specific antibody, Y174, also demonstrated GSK-3β expression in the follicles. Moreover, GSK-3β immunostaining with Y174 showed that GSK-3β colocalized with hair follicle bulge markers. Contrary to GSK-3β, GSK-3α 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-3β is expressed in hair bulge stem cells and BIO promotes the growth of ORS cells, possibly by regulating the GSK-3 signaling pathway.