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HIF‐2α/ARNT complex regulates hair development via induction of p21 Waf1/Cip1 and p27 Kip1
Author(s) -
Imamura Yuko,
Tomita Shuhei,
Imanishi Masaki,
Kihira Yoshitaka,
Ikeda Yasumasa,
Ishizawa Keisuke,
Tsuchiya Koichiro,
Tamaki Toshiaki
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-244079
Subject(s) - aryl hydrocarbon receptor nuclear translocator , physics , chemistry , microbiology and biotechnology , biology , transcription factor , gene , biochemistry , aryl hydrocarbon receptor
The hypoxia‐inducible factors HIF‐1α or HIF‐2α form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF‐1α/ARNT and HIF‐2α/ARNT complexes activate hypoxia‐inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O 2 deprivation. HIF‐2α 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‐2α/ARNT in hair development using conditional‐knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild‐type mice, HIF‐2α 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‐2α and induction of the mammalian cyclin‐dependent kinase inhibitors p21 Waf1/Cip1 and p27 Kip1 The results suggest that the HIF‐2α/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.—Imamura, Y., Tomita, S., Imanishi, M., Kihira, Y., Ikeda, Y., Ishizawa, K., Tsuchiya, K., Tamaki, T. HIF‐2α/ARNT complex regulates hair development via induction of p21 Waf1/Cip1 and p27 Kip1 . FASEB J . 28, 2517–2524 (2014). www.fasebj.org