Epidermal sensing of oxygen is essential for systemic hypoxic response.

Boutin AT, Weidemann A, Fu Z, Mesropian L, Gradin K, Jamora C, Wiesener M, Eckardt KU, Koch CJ, Ellies LG, Haddad G, Haase VH, Simon MC, Poellinger L, Powell FL, Johnson RS
Cell. 2008 133 (2): 223-34

PMID: 18423195 · PMCID: PMC2849644 · DOI:10.1016/j.cell.2008.02.038

Skin plays an essential role, mediated in part by its remarkable vascular plasticity, in adaptation to environmental stimuli. Certain vertebrates, such as amphibians, respond to hypoxia in part through the skin; but it is unknown whether this tissue can influence mammalian systemic adaptation to low oxygen levels. We have found that epidermal deletion of the hypoxia-responsive transcription factor HIF-1alpha inhibits renal erythropoietin (EPO) synthesis in response to hypoxia. Conversely, mice with an epidermal deletion of the von Hippel-Lindau (VHL) factor, a negative regulator of HIF, have increased EPO synthesis and polycythemia. We show that nitric oxide release induced by the HIF pathway acts on cutaneous vascular flow to increase systemic erythropoietin expression. These results demonstrate that in mice the skin is a critical mediator of systemic responses to environmental oxygen.

MeSH Terms (14)

Animals Blood Chemical Analysis Epidermis Erythropoietin Humans Hypoxia-Inducible Factor 1 Keratinocytes Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Nitric Oxide Oxygen Von Hippel-Lindau Tumor Suppressor Protein

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