Departmental Bulletin Paper Nfkbiz regulates the proliferation and differentiation of keratinocytes

Ishiguro-Oonuma, Toshina  ,  Ochiai, Kazuhiko  ,  Hashizume, Kazuyoshi  ,  Iwanaga, Toshihiko  ,  Morimatsu, Masami

63 ( 3 )  , pp.107 - 114 , 2015-08 , Graduate School of Veterinary Medicine, Hokkaido University
Nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) inhibitor zeta (Nfkbiz) is a nuclear inhibitor of NF-κB (IκB) protein that is also termed as molecule possessing ankyrin repeats induced by lipopolysaccharide, interleukin-1-inducible nuclear ankyrin repeat protein, or IκBζ. We found previously that disrupting the Nfkbiz gene resulted in atopic dermatitis-like lesions in mice, suggesting an important role for Nfkbiz in the skin. In this study, we examined the cellular function of Nfkbiz in keratinocytes. Immunohistochemical analyses for Ki-67 revealed that Nfkbiz-/- keratinocytes were hypoproliferative. In skin from Nfkbiz-/- mice, the expression of the keratinocyte differentiation markers K10 and filaggrin were reduced, although that of K14 was unchanged. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay revealed that the frequency of apoptosis was comparable between control and Nfkbiz-/- keratinocytes. Interestingly, the subcellular localization of the NF-κB subunits and the transcriptional activity of NF-κB were not changed in Nfkbiz-/- keratinocytes. These findings indicate a novel possible role of Nfkbiz in controlling the proliferation and differentiation of epidermal keratinocytes through NF-κB-independent mechanisms.

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