期刊
FASEB JOURNAL
卷 14, 期 5, 页码 752-760出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fasebj.14.5.752
关键词
in vivo; apoptosis; TGF-beta receptor
资金
- NCI NIH HHS [CA73796, CA 16038] Funding Source: Medline
- NIAMS NIH HHS [AR39190] Funding Source: Medline
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 beta 1 (TGF-beta 1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta 1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF-beta 1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta 1 null mice and age-matched wild-type littermates, and assessed the effects of TGF-beta 1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF-beta 1 -/- mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF-beta 1 -/- mice displayed more Ki-67-positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF-beta 1 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-beta 1-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-beta 1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TCF-beta RII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).
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