Disruption of the hedgehog signaling pathway contributes to the hair follicle cycling deficiency in Vdr knockout mice.
Mice null for the Vitamin D receptor (VdrKO) have a disrupted first hair follicle cycle and aborted subsequent hair follicle cycling. We examined the expression of different markers and mediators of hair follicle cycling in the hair follicle of the VdrKO mouse during days 13-22 when the hair follicle normally initiates and completes the first catagen. We compared the expression of those genes in mice with a nonsense mutation in hairless (Rhino), which have a similar alopecia phenotype, and to Cyp27b1 null mice which are deficient in the production of 1,25(OH)2D3, the Vdr ligand, but display normal hair follicle cycling. Our results demonstrate the down regulation of hair follicle markers and the alteration of expression of hedgehog (Hh), Wnt, Fgf, and Tgfbeta pathways in VdrKO and Rhino mice, but not in Cyp27b1KO mice. Treatment of VdrKO mice with an agonist to the Hh pathway partially restored hair follicle cycling, suggesting a role of this pathway in the regulation of hair follicle cycling by VDR. These results suggest that Vdr regulates directly or indirectly the expression of genes required for hair follicle cycling, including Hh signaling, independent of 1,25(OH)2D3.
Teichert
Arnaud
A
University of California, San Francisco, California 94121, USA.
Elalieh
Hashem
H
Bikle
Daniel
D
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002117:Calcitriol / Q000096:biosynthesis; D002453:Cell Cycle; D005786:Gene Expression Regulation / Q000502:physiology; D018859:Hair Follicle / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D053823:Hedgehog Proteins; D018167:Receptors, Calcitriol; D014157:Transcription Factors; C088661:hr protein, mouse; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol
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