| First Author | Imamura Y | Year | 2014 |
| Journal | FASEB J | Volume | 28 |
| Issue | 6 | Pages | 2517-24 |
| PubMed ID | 24599965 | Mgi Jnum | J:216543 |
| Mgi Id | MGI:5608965 | Doi | 10.1096/fj.13-244079 |
| Citation | Imamura Y, et al. (2014) HIF-2alpha/ARNT complex regulates hair development via induction of p21(Waf1/Cip1) and p27(Kip1). FASEB J 28(6):2517-24 |
| abstractText | The hypoxia-inducible factors HIF-1alpha or HIF-2alpha form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1alpha/ARNT and HIF-2alpha/ARNT complexes activate hypoxia-inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O2 deprivation. HIF-2alpha is known to regulate the function and/or differentiation of stem cells by activating the POU domain transcription factor Oct4; however, the precise underlying mechanism is unknown. This study examined the role of HIF-2alpha/ARNT in hair development using conditional-knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild-type mice, HIF-2alpha and ARNT were highly expressed in the precortex above the hair matrix, an area containing differentiating stem cells. An analysis of hair size and type in these mice showed that loss of ARNT decreased the production of zigzag hairs, corresponding to reduced expression of HIF-2alpha and induction of the mammalian cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27 (Kip1). The results suggest that the HIF-2alpha/ARNT complex regulates hair follicle differentiation via induction of p21(Waf1/Cip1) and possibly p27(Kip1), as p27(Kip1) expression was not altered in ARNT knockout mice. The findings provide insight into a possible mechanism underlying hair growth disorders and can be useful for future studies on hair follicle response to insults, such as chemotherapy and ionizing radiation. |
