@article{fa503d68bccd48cf92a6f652147e6940,
title = "Epidermal Sensing of Oxygen Is Essential for Systemic Hypoxic Response",
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-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.",
keywords = "HUMDISEASE, SIGNALING",
author = "Boutin, {Adam T.} and Alexander Weidemann and Zhenxing Fu and Lernik Mesropian and Katarina Gradin and Colin Jamora and Michael Wiesener and Eckardt, {Kai Uwe} and Koch, {Cameron J.} and Ellies, {Lesley G.} and Gabriel Haddad and Haase, {Volker H.} and Simon, {M. Celeste} and Lorenz Poellinger and Powell, {Frank L.} and Johnson, {Randall S.}",
note = "Funding Information: We thank Steven Elliott, Gloria Biddlecome, and Susan Swift of Amgen, Inc. for insightful advice and discussions. We thank Wayne McNulty and Courtney Corle for excellent technical assistance and members of the Poellinger and Johnson Laboratories as well as numerous other colleagues for helpful suggestions, with a particular thanks to Victor Nizet for assistance with nitroglycerin delivery and pharmacology. This work was supported in part by NIH grant K22CA118182 to L.G.E. and NIH grants R01AI060840 and R01CA082515 and support from the STINT and Wennergren Foundations to R.S.J. A.W. was supported by the German Research Foundation (DFG WE4275/1-1). ",
year = "2008",
month = apr,
day = "18",
doi = "10.1016/j.cell.2008.02.038",
language = "English (US)",
volume = "133",
pages = "223--234",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}