title: Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo.
abstract: The regression phase of the hair cycle (catagen) is an apoptosis-driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor beta1 (TGF-beta1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF-beta1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta1 null mice and age-matched wild-type littermates, and assessed the effects of TGF-beta1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF-beta1 -/- mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF-beta1-/- mice displayed more Ki-67-positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF-beta1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratinocytes was reduced and the number of TUNEL + cells was increased in the TGF-beta1-treated mice compared to controls. Double visualization of TGF-beta type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF-beta1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TGF-betaRII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA. Department of Dermatology, University Hospital Eppendorf, University of Hamburg, D-20246 Hamburg, Germany. Departme.
authors.forename: K
authors.initials: K
authors.lastname: Foitzik
authors.forename: G
authors.initials: G
authors.lastname: Lindner
authors.forename: S
authors.initials: S
authors.lastname: Mueller-Roever
authors.forename: M
authors.initials: M
authors.lastname: Maurer
authors.forename: N
authors.initials: N
authors.lastname: Botchkareva
authors.forename: V
authors.initials: V
authors.lastname: Botchkarev
authors.forename: B
authors.initials: B
authors.lastname: Handjiski
authors.forename: M
authors.initials: M
authors.lastname: Metz
authors.forename: T
authors.initials: T
authors.lastname: Hibino
authors.forename: T
authors.initials: T
authors.lastname: Soma
authors.forename: G P
authors.initials: GP
authors.lastname: Dotto
authors.forename: R
authors.initials: R
authors.lastname: Paus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D018859:Hair Follicle / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta