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PMID: 16702408 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Keratin 17 modulates hair follicle cycling in a TNFalpha-dependent fashion.

Genes & development ·Vol. 20 ·No. 10 ·2006-05-15 ·Pages 1353-64

Tong X, Coulombe PA

Abstract

Mammalian hair follicles cycle between stages of rapid growth (anagen) and metabolic quiescence (telogen) throughout life. Transition from anagen to telogen involves an intermediate stage, catagen, consisting of a swift, apoptosis-driven involution of the lower half of the follicle. How catagen is coordinated, and spares the progenitor cells needed for anagen re-entry, is poorly understood. Keratin 17 (K17)-null mice develop alopecia in the first week post-birth, correlating with hair shaft fragility and untimely apoptosis in the hair bulb. Here we show that this abnormal apoptosis reflects premature entry into catagen. Of the proapoptotic challenges tested, K17-null skin keratinocytes in primary culture are selectively more sensitive to TNFalpha. K17 interacts with TNF receptor 1 (TNFR1)-associated death domain protein (TRADD), a death adaptor essential for TNFR1-dependent signal relay, suggesting a functional link between this keratin and TNFalpha signaling. The activity of NF-kappaB, a downstream target of TNFalpha, is increased in K17-null skin. We also find that TNFalpha is required for a timely anagen-catagen transition in mouse pelage follicles, and that its ablation partially rescues the hair cycling defect of K17-null mice. These findings identify K17 and TNFalpha as two novel and interdependent regulators of hair cycling.

MeSH Terms
Alopecia/genetics Animals Apoptosis/genetics Cell Cycle/genetics Hair Follicle/cytology,growth & development,metabolism Keratinocytes/cytology,metabolism Keratins/genetics,metabolism Mice Mice, Mutant Strains NF-kappa B/metabolism Signal Transduction TNF Receptor-Associated Death Domain Protein Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism Tumor Necrosis Factor-alpha/genetics,metabolism
Chemicals
Krt17 protein, mouse NF-kappa B TNF Receptor-Associated Death Domain Protein Tradd protein, mouse Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Tumor Necrosis Factor-alpha Keratins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tong Xuemei
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Coulombe Pierre A
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1387406
Published
2006-05-15
Pages
1353-64
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1472909
Subset
IM
Grants
NIAMS NIH HHS · R01 AR044232 · United States
NIAMS NIH HHS · AR44232 · United States
External Links
PubMed source DOI: 10.1101/gad.1387406 PMC Full Text View journal details
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