microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation

• DOI: 10.1073/pnas.1111292109
• Publication Date: 2012-08-14T02:37:49Z
• Authors: Han Peng; Nihal Kaplan; Robert B. Hamanaka; Julia Katsnelson; Hanz Blatt; Wending Yang; Liangliang Hao; Paul J. Bryar; Randall S. Johnson; Spiro Getsios; Navdeep S. Chandel; Robert M. Lavker
• Keywords: Epidermis (zoology)

Notch plays a critical role in the transition from proliferation to differentiation epidermis and corneal epithelium. Furthermore, aberrant signaling is feature of diseases like psoriasis, eczema, nonmelanoma skin cancer, melanoma where are impaired. Whereas much known about downstream events following signaling, factors responsible for negatively regulating receptor after ligand activation incompletely understood. can undergo hydroxylation by factor-inhibiting hypoxia-inducible factor 1 (FIH-1); however, biological significance this phenomenon unclear. Here we show that FIH-1 expression up-regulated diseased Elevating levels primary human epidermal keratinocytes (HEKs) epithelial (HCEKs) impairs submerged cultures “three-dimensional” organotypic raft model epidermis, part, via coordinate decrease signaling. Knockdown enhances keratinocyte differentiation. Loss vivo increased activity limbal epithelium, resulting more differentiated phenotype. microRNA-31 (miR-31) an endogenous negative regulator results differentiation, mediated activation. Ectopically expressing miR-31 undifferentiated cell line promotes recapitulates epithelium three-dimensional culture model. Our define previously unknown mechanism fate decisions potential is, controlled through miR-31/FIH-1 nexus.