Nuclear Factor I-C Regulates TGF-beta-dependent Hair Follicle Cycling

作者:P****ri Genta; Edelmann Simone; Hoegger Florence; Dusserre Yves; Mermod Nicolas*; Calabrese Alessandra
来源:JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285(44): 34115-34125.
DOI:10.1074/jbc.M110.120659

摘要

Skin appendages such as teeth and hair share several common signaling pathways. The nuclear factor IC(NFI-C) transcription factor has been implicated in tooth development, but a potential role in hair growth had not been assessed. In this study we found that NFI-C regulates the onset of the hair growth cycle. NFIC(-/-) mice were delayed in the transition from the telogen to anagen phase of the hair follicle cycle after either experimental depilation or spontaneous hair loss. Lack of NFI-C resulted in delayed induction of the sonic hedgehog, Wnt5a, and Lef1 gene expression, which are key regulators of the hair follicle growth initiation. NFI-C(-/-) mice also showed elevated levels of transforming growth factor beta 1 (TGF-beta 1), an inhibitor of keratinocyte proliferation, and of the cell cycle inhibitor p21 at telogen. Reduced expression of Ki67, a marker of cell proliferation, was noted at the onset of anagen, indicating impaired activation of the hair progenitor cells. These findings implicate NFI-C in the repression of TGF-beta 1 signaling during telogen stage, resulting in the delay of progenitor cell proliferation and hair follicle regeneration in NFI-C-deficient mice. Taken together with prior observations, these findings also designate NFI-C as a regulator of adult progenitor cell proliferation and of postnatal tissue growth or regeneration.

  • 出版日期2010-10-29