期刊
CELL
卷 133, 期 2, 页码 223-234出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.02.038
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资金
- NCI NIH HHS [R01CA082515, R01 CA100787, R01 CA082515, R01 CA082515-09, K22CA118182] Funding Source: Medline
- NHLBI NIH HHS [R01 HL081823] Funding Source: Medline
- NIAID NIH HHS [R01AI060840] Funding Source: Medline
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-1 alpha inhibits renal erythropoietin (EPO) synthesis in response to hypoxia. Conversely, mice with an epidermal deletion of the vonHippel-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.
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