Kim Bong-Kyu, Yoon Sungjoo Kim
Department of Medical Life Science, The Catholic University of Korea, Seoul, Korea.
J Cell Physiol. 2015 Sep;230(9):2075-85. doi: 10.1002/jcp.24935.
Hairless (HR) has been shown to regulate hair follicle (HF) morphogenesis and hair cycling. The Hr mutant hair loss mouse referred to as "hairpoor" (Hr(Hp)) displays overexpression of the HR protein through translational derepression. In this study, we found that 64 miRNAs were differentially expressed between the skin of Hr(Hp)/Hr(Hp) and wild type mice at P7 using miRNA-microarray analysis and miR-31 displayed the most reduced expression in Hr(Hp)/Hr(Hp) skin. In vivo observation and investigation using an in vitro reporter expression system revealed that miR-31 and pri-miR-31 were consistently down-regulated in the HR over-expressed condition. In addition, we found that the transforming growth factor β2 (Tgf-β2), a known catagen inducer, is the putative target of miR-31. Furthermore, Tgf-β2 level was also increased in HR over-expressed keratinocyte and Hr(Hp)/Hr(Hp) mice. These study results suggest that HR controls Tgf-β2 expression via regulation of miR-31, thus causing abnormal hair cycle in Hr(Hp)/Hr(Hp) mice.
无毛基因（HR）已被证明可调节毛囊（HF）形态发生和毛发周期。被称为“毛发稀少”（Hr(Hp)）的Hr突变体脱发小鼠通过翻译抑制解除表现出HR蛋白的过表达。在本研究中，我们使用miRNA微阵列分析发现，在出生后第7天，Hr(Hp)/Hr(Hp)小鼠与野生型小鼠皮肤之间有64种miRNA差异表达，且miR-31在Hr(Hp)/Hr(Hp)皮肤中的表达降低最为明显。使用体外报告基因表达系统进行的体内观察和研究表明，在HR过表达条件下，miR-31和pri-miR-31持续下调。此外，我们发现已知的退行期诱导因子转化生长因子β2（Tgf-β2）是miR-31的假定靶标。此外，在HR过表达的角质形成细胞和Hr(Hp)/Hr(Hp)小鼠中，Tgf-β2水平也升高。这些研究结果表明，HR通过调节miR-31来控制Tgf-β2的表达，从而导致Hr(Hp)/Hr(Hp)小鼠毛发周期异常。
