title: Functional role of beta 1 integrin-mediated signalling in the human hair follicle.
abstract: Integrins are transmembrane adhesion proteins that convey critical topobiological information and exert crucial signalling functions. In skin and hair follicle biology, beta1 integrins and their ligands are of particular interest. It is not yet known whether beta1 integrins play any role in the regulation of human hair growth and the expression pattern of beta1 integrin in the human pilosebaceous unit remains ill-defined. Here, we show that pilosebaceous immunoreactivity for beta1 integrin is most prominent in the outermost layer of the outer root sheath and the surrounding connective tissue sheath of human scalp hair follicles in situ and in vitro. Sites of beta1 integrin immunoreactivity co-express fibronectin and tenascin-C. Contrary to previous reports, beta1 integrin immunoreactivity in situ was not significantly upregulated in the human bulge region. Functionally, two beta1 integrin-activating antibodies (12G10, TS2/16) and ligand-mimicking RGD peptides promoted the growth of microdissected, organ-cultured human scalp hair follicles in vitro and inhibited spontaneous hair follicle regression. This supports the concept that beta1 integrin-mediated signalling is also important in human hair growth control. The physiologically relevant organ culture assay employed here is a potential research tool for exploring whether targeted stimulation of beta1 integrin-mediated signalling is a suitable candidate for human hair loss management.
authors.affiliation: Department of Dermatology, Allergology and Venerology, University Hospital of Schleswig-Holstein, University of Lübeck, Lübeck, Germany. Jennifer.Kloepper@uk-sh.de <Jennifer.Kloepper@uk-sh.de>
authors.forename: J E
authors.initials: JE
authors.lastname: Kloepper
authors.forename: S
authors.initials: S
authors.lastname: Hendrix
authors.forename: E
authors.initials: E
authors.lastname: Bodó
authors.forename: S
authors.initials: S
authors.lastname: Tiede
authors.forename: M J
authors.initials: MJ
authors.lastname: Humphries
authors.forename: M P
authors.initials: MP
authors.lastname: Philpott
authors.forename: R
authors.initials: R
authors.lastname: Fässler
authors.forename: R
authors.initials: R
authors.lastname: Paus
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001681:Biological Assay / Q000379:methods; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006197:Hair / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018859:Hair Follicle / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D019063:Tenascin / Q000378:metabolism
chemical_list: D000906:Antibodies; D005353:Fibronectins; D019012:Integrin beta1; D008024:Ligands; D010455:Peptides; D019063:Tenascin