Hairless Up-Regulates Tgf-β2 Expression via Down-Regulation of miR-31 in the Skin of "Hairpoor" (HrHp) Mice.

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.

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