Department of Biochemistry and Molecular Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Nutrition and Food Sciences, Texas Woman's University, Denton, TX, USA.
Commun Biol. 2024 Apr 12;7(1):453. doi: 10.1038/s42003-024-06160-2.
The hair follicle (HF) is a self-renewing adult miniorgan that undergoes drastic metabolic and morphological changes during precisely timed cyclic organogenesis. The HF cycle is known to be regulated by steroid hormones, growth factors and circadian clock genes. Recent data also suggest a role for a vitamin A derivative, all-trans-retinoic acid (ATRA), the activating ligand of transcription factors, retinoic acid receptors, in the regulation of the HF cycle. Here we demonstrate that ATRA signaling cycles during HF regeneration and this pattern is disrupted by genetic deletion of epidermal retinol dehydrogenases 2 (RDHE2, SDR16C5) and RDHE2-similar (RDHE2S, SDR16C6) that catalyze the rate-limiting step in ATRA biosynthesis. Deletion of RDHEs results in accelerated anagen to catagen and telogen to anagen transitions, altered HF composition, reduced levels of HF stem cell markers, and dysregulated circadian clock gene expression, suggesting a broad role of RDHEs in coordinating multiple signaling pathways.
毛囊（HF）是一种自我更新的成人小器官，在精确计时的周期性器官发生过程中经历剧烈的代谢和形态变化。HF 周期已知受类固醇激素、生长因子和昼夜节律基因的调节。最近的数据还表明，维生素 A 衍生物全反式视黄酸（ATRA），即转录因子视黄酸受体的激活配体，在 HF 周期的调节中起作用。在这里，我们证明 ATRA 信号在 HF 再生过程中循环，这种模式被表皮视黄醇脱氢酶 2（RDHE2，SDR16C5）和 RDHE2 样（RDHE2S，SDR16C6）的基因缺失破坏，这些酶催化 ATRA 生物合成的限速步骤。RDHE 的缺失导致生长期到退行期和退行期到生长期的过渡加速，HF 组成改变，HF 干细胞标志物水平降低，昼夜节律基因表达失调，表明 RDHE 在协调多种信号通路方面发挥广泛作用。
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