Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion
Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion
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DOI：
10.1101/gad.1387406
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发表时间：
2006-05-15
影响因子：
10.5
通讯作者：
Coulombe, Pierre A.
中科院分区：
文献类型：
--
作者：
Tong, Xuemei;Coulombe, Pierre A.
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 TNF alpha. 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 TNF alpha signaling. The activity of NF-kappa B, a downstream target of TNF alpha, is increased in K17-null skin. We also find that TNF alpha 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 TNF alpha as two novel and interdependent regulators of hair cycling.
