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Publication : Hypoxia-inducible factor-2α-dependent hypoxic induction of Wnt10b expression in adipogenic cells.

First Author  Park YK Year  2013
Journal  J Biol Chem Volume  288
Issue  36 Pages  26311-22
PubMed ID  23900840 Mgi Jnum  J:203532
Mgi Id  MGI:5527211 Doi  10.1074/jbc.M113.500835
Citation  Park YK, et al. (2013) Hypoxia-inducible factor-2alpha-dependent hypoxic induction of Wnt10b expression in adipogenic cells. J Biol Chem 288(36):26311-22
abstractText  Adipocyte hyperplasia and hypertrophy in obesity can lead to many changes in adipose tissue, such as hypoxia, metabolic dysregulation, and enhanced secretion of cytokines. In this study, hypoxia increased the expression of Wnt10b in both human and mouse adipogenic cells, but not in hypoxia-inducible factor (HIF)-2alpha-deficient adipogenic cells. Chromatin immunoprecipitation analysis revealed that HIF-2alpha, but not HIF-1alpha, bound to the Wnt10b enhancer region as well as upstream of the Wnt1 gene, which is encoded by an antisense strand of the Wnt10b gene. Hypoxia-conditioned medium (H-CM) induced phosphorylation of lipoprotein-receptor-related protein 6 as well as beta-catenin-dependent gene expression in normoxic cells, which suggests that H-CM contains canonical Wnt signals. Furthermore, adipogenesis of both human mesenchymal stem cells and mouse preadipocytes was inhibited by H-CM even under normoxic conditions. These results suggest that O2 concentration gradients influence the formation of Wnt ligand gradients, which are involved in the regulation of pluripotency, cell proliferation, and cell differentiation.
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