Epidermal sensing of oxygen is essential for systemic hypoxic response

被引：142

作者：

Boutin, Adam T. ^{[1
]}

Weidemann, Alexander ^{[1
]}

Fu, Zhenxing ^{[5
,6
,7
]}

Mesropian, Lernik ^{[1
]}

Gradin, Katarina ^{[2
]}

Jamora, Colin ^{[1
]}

Wiesener, Michael ^{[3
]}

Eckardt, Kai-Uwe ^{[3
]}

Koch, Cameron J. ^{[4
]}

Ellies, Lesley G. ^{[5
,6
,7
]}

Haddad, Gabriel ^{[5
,6
,7
]}

Haase, Volker H. ^{[4
]}

Simon, M. Celeste ^{[4
]}

Poellinger, Lorenz ^{[2
]}

Powell, Frank L. ^{[5
,6
,7
]}

Johnson, Randall S. ^{[1
]}

机构：

[1] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA

[2] Karolinska Inst, S-17177 Stockholm, Sweden

[3] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany

[4] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[5] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA

来源：

CELL | 2008年 / 133卷 / 02期

关键词：

D O I：

10.1016/j.cell.2008.02.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：223 / 234

页数：12

共 52 条

[1] PLASMA ERYTHROPOIETIN IN MEN AND MICE DURING ACCLIMATIZATION TO DIFFERENT ALTITUDES
ABBRECHT, PH
KITTELL, JK
[J]. JOURNAL OF APPLIED PHYSIOLOGY, 1972, 32 (01) : 54 - &
[2] Bergmann C., 1848, VERHALTNISSE WARMEOK
[3] Enhanced erythropoietin production during hypobaric hypoxia in mice under treatments to keep the erythrocyte mass from rising:: Implications for the adaptive role of polycythemia
Bozzini, CE
Barceló, AC
Conti, MI
Martínez, MP
Alippi, RM
[J]. HIGH ALTITUDE MEDICINE & BIOLOGY, 2005, 6 (03) : 238 - 246
[4] Role of hypoxia-inducible factor (HIF)-1α-versus HIF-2α in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-1, or loss of von Hippel-Lindau function:: Implications for targeting the HIF pathway
Carroll, Veronica A.
Ashcroft, Margaret
[J]. CANCER RESEARCH, 2006, 66 (12) : 6264 - 6270
[5] DURAND J, 1969, FED PROC, V28, P1124
[6] Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α
Elson, DA
Thurston, G
Huang, LE
Ginzinger, DG
McDonald, DM
Johnson, RS
Arbeit, JM
[J]. GENES & DEVELOPMENT, 2001, 15 (19) : 2520 - 2532
[7] Oxygen levels in normal and previously irradiated human skin as assessed by EF5 binding
Evans, Sydney M.
Schrlau, Amy E.
Chalian, Ara A.
Zhang, Paul
Koch, Cameron J.
[J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (12) : 2596 - 2606
[8] Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression
Fandrey, J
[J]. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2004, 286 (06) : R977 - R988
[9] Newborn care practices in low socioeconomic settlements of Karachi, Pakistan
Fikree, FF
Ali, TS
Durocher, JM
Rahbar, MH
[J]. SOCIAL SCIENCE & MEDICINE, 2005, 60 (05) : 911 - 921
[10] Gassmann M, 2003, ADV EXP MED BIOL, V543, P323

← 1 2 3 4 5 6 →