Hairless Up‐Regulates Tgf‐β2 Expression via Down‐Regulation of miR‐31 in the Skin of “Hairpoor” (Hr^Hp) Mice

Abstract

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.

The major miR‐31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation

“…During hair growth (anagen phase of the hair growth cycle) keratinocytes are activated and, in coordination with the dermal papilla, rebuild a hair shaft “factory”, known as the anagen hair follicle. Interestingly, miR‐31 is one of the few microRNAs associated with anagen (Figure B) . Furthermore, miR‐31 is upregulated in human basal cell carcinomas (BCCs), a tumor type with activated keratinocytes that exhibits hair follicle differentiation features (Figure C; Student's t ‐test P =.008; Fig.…”

“…Interestingly, miR-31 is one of the few microRNAs associated with anagen ( Figure 1B). [13,23] Furthermore, miR-31 is upregulated in human basal cell carcinomas (BCCs), a tumor type with activated keratinocytes that exhibits hair follicle differentiation features ( Figure 1C; Student's t-test P=.008; Fig. S1B).…”

Perspectives on miRNAs Targeting DKK1 for Developing Hair Regeneration Therapy

“…These mice exhibit hair loss and overexpression of protein hairless. The study demonstrated that the miR-31 level was significantly downregulated in the skin of Hr Hp / Hr Hp mice [ 204 ].…”

The Molecular Revolution in Cutaneous Biology: Noncoding RNAs: New Molecular Players in Dermatology and Cutaneous Biology

“…miR-31 inhibits the growth phase of the hair cycle by modulating the activity of the bone morphogenic protein and fibroblast growth factor signaling pathways (Mardaryev et al, 2010). The crucial importance of miR-31 in HF maintenance and cycling was further shown by the notion that HF degradation in "hairpoor"-that is, Hr(Hp)-mice is associated with transcriptional downregulation of miR-31 and subsequent induction of transforming growth factor-b2 signaling (Kim and Yoon, 2015).…”