Dietary vitamin A regulates wingless-related MMTV integration site signaling to alter the hair cycle

Hair follicles cycle through periods of growth (anagen), regression (catagen), rest (telogen), and release (exogen). Telogen is further divided into refractory and competent telogen based on expression of bone morphogenetic protein 4 (BMP4) and wingless-related MMTV integration site 7A (WNT7A). During refractory telogen hair follicle stem cells (HFSC) are inhibited. Retinoic acid synthesis proteins localized to the hair follicle and this localization pattern changed throughout the hair cycle. In addition, excess retinyl esters arrested hair follicles in telogen. The purpose of this study was to further define these hair cycle changes. BMP4 and WNT7A expression was also used to distinguish refractory from competent telogen in C57BL/6J mice fed different levels of retinyl esters from two previous studies. These two studies produced opposite results; and differed in the amount of retinyl esters the dams consumed and the age of the mice when the different diet began. There were a greater percentage of hair follicles in refractory telogen both when mice were bred on an unpurified diet containing copious levels of retinyl esters (study 1) and consumed excess levels of retinyl esters starting at 12 weeks of age, as well as when mice were bred on a purified diet containing adequate levels of retinyl esters (study 2) and remained on this diet at 6 weeks of age. WNT7A expression was consistent with these results. Next, the localization of vitamin A metabolism proteins in the two stages of telogen was examined. Keratin 6 (KRT6) and cellular retinoic acid binding protein 2 (CRABP2) localized almost exclusively to refractory telogen hair follicles in study 1. However, KRT6 and CRABP2 localized to both competent and refractory telogen hair follicles in mice fed adequate and high levels of retinyl esters in study 2. In mice bred and fed an unpurified diet retinol dehydrogenase SDR16C5, retinal dehydrogenase 2 (ALDH1A2), and cytochrome p450 26B1 (CYP26B1), enzymes and proteins involved in RA metabolism, localized to BMP4 positive refractory telogen hair follicles. This suggests that vitamin A may contribute to the inhibition of HFSC during refractory telogen in a dose dependent manner.

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Vitamin A Metabolism During Refractory Telogen

Current Developments in Nutrition ◽

10.1093/cdn/nzaa041_013 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 109-109

Author(s):

Damla Hovland ◽

Liye Suo ◽

Natalia Kedishvili ◽

John Sundberg ◽

Helen Everts

Keyword(s):

Vitamin A ◽

Hair Follicles ◽

Dietary Vitamin ◽

Hair Cycle ◽

Retinol Dehydrogenase ◽

Vitamin A Metabolism ◽

Funding Sources ◽

Morphogenetic Protein ◽

Bmp4 Expression ◽

Complete Set

Abstract Objectives Hair follicles cycle through periods of growth (anagen), regression (catagen) and rest (telogen). Telogen is further divided into refractory and competent telogen based on the expression of bone morphogenetic protein 4 (BMP4). Previously, the expression of a complete set of proteins involved in retinoic acid (RA) synthesis and signaling localized to the hair follicle and changed throughout the hair cycle. In addition, excess dietary vitamin A arrested the hair cycle in telogen; while retinol dehydrogenases short-chain dehydrogenase/reductase family 16C members 5 and 6 (Sdr16c5−/−/Sdr16c6−/−) double null mice had an accelerated the hair cycle. The purpose of this study was to further define these changes in the hair cycle. Methods The localization of RA synthesis proteins SDR16C5, retinol dehydrogenase 10 (RDH10), retinal dehydrogenase 2 (ALDH1A2), cellular RA binding protein 2 (CRABP2), RA degradation enzyme cytochrome p450 26B1 (CYP26B1), and BMP4 was examined in telogen hair follicles in female C57BL/6 J mice by immunohistochemistry. Immunohistochemistry with an antibody against BMP4 was also used to mark refractory telogen in the previous dietary vitamin A study. Results All proteins localized to BMP4 positive refractory telogen hair follicles. SDR16C5 and ALDH1A2 were also seen in BMP4 negative competent telogen hair follicles, but at a lower level. RDH10 was expressed in both BMP4 negative and positive hair follicles at similar levels. BMP4 expression was also used to distinguish refractory from competent telogen in C57BL/6 J mice fed different levels of vitamin A. Both low and excess dietary vitamin A resulted a greater percentage of hair follicles in refractory telogen in different studies. Conclusions In conclusion, RA synthesis and signaling may be stronger in refractory telogen and contribute to the inhibition of the hair cycle. Funding Sources NIH/NIAMS, Internal funding.

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Dietary vitamin A supplementation in rats: suppression of leptin and induction of UCP1 mRNA

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)32117-9 ◽

1999 ◽

Vol 40 (5) ◽

pp. 824-829 ◽

Cited By ~ 1

Author(s):

Monica V. Kumar ◽

Gregory D. Sunvold ◽

Philip J. Scarpace

Keyword(s):

Vitamin A ◽

Dietary Vitamin ◽

Vitamin A Supplementation

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The complexity of producing and interpreting dietary vitamin A statistics

Journal of Food Composition and Analysis ◽

10.1016/j.jfca.2021.103926 ◽

2021 ◽

pp. 103926

Author(s):

Ana Moltedo ◽

Cristina Álvarez-Sánchez ◽

Fernanda Grande ◽

Ruth Charrondiere

Keyword(s):

Vitamin A ◽

Dietary Vitamin

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Maternal dietary intake of vitamin A during pregnancy was inversely associated with congenital diaphragmatic hernia: the Japan Environment and Children’s Study

British Journal Of Nutrition ◽

10.1017/s0007114519002204 ◽

2019 ◽

Vol 122 (11) ◽

pp. 1295-1302 ◽

Cited By ~ 2

Author(s):

Takehiro Michikawa ◽

Shin Yamazaki ◽

Makiko Sekiyama ◽

Tatsuo Kuroda ◽

Shoji F. Nakayama ◽

...

Keyword(s):

Vitamin A ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Dietary Habits ◽

Daily Intake ◽

First Trimester ◽

Dietary Vitamin ◽

Birth Cohort Study ◽

Case Control Studies ◽

Total Vitamin

AbstractThe pathogenesis of congenital diaphragmatic hernia (CDH) is largely unknown; however, vitamin A seems to play a role in diaphragmatic development. Previous case–control studies reported that maternal dietary vitamin A intake was inversely associated with the risk of CDH. To our knowledge, however, there is no prospective evidence regarding this association. Our aim was to examine whether maternal intake of vitamin A was associated with CDH occurrence. Baseline data, from the Japan nationwide birth cohort study (2011–2014) of 89 658 mothers (mean age at delivery = 31·2 years) who delivered singleton live births, were analysed. We assessed dietary habits using an FFQ focused on the first trimester and estimated the daily intake of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids and vegetables. The occurrence of CDH was ascertained from medical records. A total of forty cases of CDH were documented. The adjusted OR of CDH occurrence for the high total vitamin A intake category (median = 468 μg/d) was 0·6 (95 % CI 0·3, 1·2) with reference to the low intake category (230 μg/d). When we restricted to mothers with a prepregnancy BMI of 18·5–24·9 kg/m2, vitamin A intake was inversely associated with the risk of their children being born with CDH (OR 0·5, 95 % CI 0·2, 1·0). Even given the limited number of cases in the study, our findings provide additional evidence to link vitamin A with CDH.

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