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. 2015 May;240(5):618-23.
doi: 10.1177/1535370214557220. Epub 2014 Oct 30.

Dietary Vitamin A Regulates Wingless-Related MMTV Integration Site Signaling to Alter the Hair Cycle

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Free PMC article

Dietary Vitamin A Regulates Wingless-Related MMTV Integration Site Signaling to Alter the Hair Cycle

Liye Suo et al. Exp Biol Med (Maywood). .
Free PMC article

Abstract

Alopecia areata (AA) is an autoimmune hair loss disease caused by a cell-mediated immune attack of the lower portion of the cycling hair follicle. Feeding mice 3-7 times the recommended level of dietary vitamin A accelerated the progression of AA in the graft-induced C3H/HeJ mouse model of AA. In this study, we also found that dietary vitamin A, in a dose dependent manner, activated the hair follicle stem cells (SCs) to induce the development and growth phase of the hair cycle (anagen), which may have made the hair follicle more susceptible to autoimmune attack. Our purpose here is to determine the mechanism by which dietary vitamin A regulates the hair cycle. We found that vitamin A in a dose-dependent manner increased nuclear localized beta-catenin (CTNNB1; a marker of canonical wingless-type Mouse Mammary Tumor Virus integration site family (WNT) signaling) and levels of WNT7A within the hair follicle bulge in these C3H/HeJ mice. These findings suggest that feeding mice high levels of dietary vitamin A increases WNT signaling to activate hair follicle SCs.

Keywords: Dietary vitamin A; WNT; hair cycling; hair follicle stem cell.

Figures

Figure 1
Figure 1
Dietary vitamin A dose dependently altered nuclear localized CTNNB1 and WNT7A in telogen hair follicles of C3H/HeJ mice. Immunohistochemistry was performed with antibodies against CTNNB1 (a–e), WNT7A (f–j), and WNT7B (k–o) in dorsal skin from C3H/HeJ mice fed 0 (a, f, k), 4 (b, g, l), 12 (c, h, m), and 28 (d, i, n) IU vitamin A/g diet. Blinded IHC score for CTNNB1 and WNT7A, WNT7B were calculated as the immunoreactivity (IR) measured on a 0–4 scale multiplied by the fraction of cells within the telogen hair follicle and the fraction of telogen hair follicles. Mean ± SD. Different letters are significantly different, P < 0.05. Bar = 10.1 μM
Figure 2
Figure 2
Dietary vitamin A did not significantly altered BMP4 or TGFB2 in telogen hair follicles of C3H/HeJ mice. Immunohistochemistry was performed with antibodies against BMP4 (a–e) and TGFB2 (f–j) in dorsal skin from C3H/HeJ mice fed 0 (a, f), 4 (b, g), 12 (c, h), and 28 (d, i) IU vitamin A/g diet. A blinded IHC score of BMP4 was measured using the total number of BMP4 positive cells in the dermis around telogen hair follicles divided by the number of telogen hair follicles. Blinded IHC score for TGFB2 was calculated as the immunoreactivity (IR) measured on a 0–4 scale multiplied by the fraction of cells within the telogen hair follicle and the fraction of telogen hair follicles. Mean ± SD. Bar = 10.1 μM

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