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Hypoxia up‐regulates the angiogenic cytokine secretoneurin via an HIF‐1α‐ and basic FGF‐dependent pathway in muscle cells
Author(s) -
Egger Margot,
Schgoer Wilfried,
Beer Arno G. E.,
Jeschke Johannes,
Leierer Johannes,
Theurl Markus,
Frauscher Silke,
Tepper Oren M.,
Niederwanger Andreas,
Ritsch Andreas,
Kearney Marianne,
Wanschitz Julia,
Gurtner Geoffrey C.,
FischerColbrie Reiner,
Weiss Guenter,
PizaKatzer Hildegunde,
Losordo Douglas W.,
Patsch Josef R.,
Schratzberger Peter,
Kirchmair Rudolf
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7440com
Subject(s) - hypoxia (environmental) , biology , vascular endothelial growth factor , hypoxia inducible factors , basic fibroblast growth factor , chemistry , microbiology and biotechnology , medicine , cancer research , endocrinology , growth factor , receptor , biochemistry , organic chemistry , oxygen , gene , vegf receptors
Expression of angiogenic cytokines like vascular endothelial growth factor is enhanced by hypoxia. We tested the hypothesis that decreased oxygen levels up‐regulate the angiogenic factor sec‐retoneurin. In vivo, muscle cells of mouse ischemic hind limbs showed increased secretoneurin expression, and inhibition of secretoneurin by a neutralizing antibody impaired the angiogenic response in this ischemia model. In a mouse soft tissue model of hypoxia, secretoneurin was increased in subcutaneous muscle fibers. In vitro, secretoneurin mRNA and protein were up‐regulated in L6 myoblast cells after exposure to low oxygen levels. The hypoxia‐depen‐dent regulation of secretoneurin was tissue specific and was not observed in endothelial cells, vascular smooth muscle cells, or AtT20 pituitary tumor cells. The hypoxia‐dependent induction of secretoneurin in L6 myoblasts is regulated by hypoxia‐inducible factor‐la, since inhibition of this factor using si‐RNA inhibited up‐regulation of secretoneurin. Induction of secretoneurin by hypoxia was dependent on basic fibroblast growth factor in vivo and in vitro, and inhibition of this regulation by heparinase suggests an involvement of low‐affinity basic fibroblast growth factor binding sites. In summary, our data show that the angiogenic cytokine secretoneurin is up‐regulated by hypoxia in muscle cells by hypoxia‐inducible factor‐1α‐ and basic fibroblast growth factor‐dependent mechanisms.—Egger, M., Schgoer, W., Beer, A. G. E., Jeschke, J., Leierer, J., Theurl, M., Frauscher, S., Tepper, O. M., Niederwanger, A., Ritsch, A., Kearney, M., Wanschitz, J., Gurtner, G. C., Fischer‐Colbrie, R., Weiss, G., Piza‐Katzer, H., Losordo, D. W., Patsch, J. R., Schratzberger, P., Kirchmair, R. Hypoxia up‐regulates the angiogenic cytokine secretoneurin via an HIF‐1α‐ and basic FGF‐dependent pathway in muscle cells. FASEB J. 21, 2906–2917 (2007)