西亚试剂：Epidermal Sensing of Oxygen Is Essential for Systemic Hypox

Epidermal Sensing of Oxygen Is Essential for Systemic Hypoxic Response
Adam T. Boutin,1 Alexander Weidemann,1 Zhenxing Fu,5 Lernik Mesropian,1 Katarina Gradin,2 Colin Jamora,1 Michael Wiesener,3 Kai-Uwe Eckardt,3 Cameron J. Koch,4 Lesley G. Ellies,5 Gabriel Haddad,5 Volker H. Haase,4 M. Celeste Simon,4 Lorenz Poellinger,2 Frank L. Powell,5 and Randall S. Johnson1,

1 Molecular Biology Section, Division of Biological Sciences, UC San Diego, La Jolla, CA 92093, USA
2 Karolinska Institute, Stockholm S-17177, Sweden
3 University of Erlangen, Erlangen D-91054, Germany
4 University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
5 Departments of Medicine, Pediatrics, and Pathology, UC San Diego School of Medicine, La Jolla 92093 CA, USA

Summary
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-1α 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.

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