Format

Send to

Choose Destination
Cell. 2008 Apr 18;133(2):223-34. doi: 10.1016/j.cell.2008.02.038.

Epidermal sensing of oxygen is essential for systemic hypoxic response.

Author information

1
Molecular Biology Section, Division of Biological Sciences, UC San Diego, La Jolla, CA 92093, USA.

Abstract

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.

Comment in

PMID:
18423195
PMCID:
PMC2849644
DOI:
10.1016/j.cell.2008.02.038
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center