Hypoxia up-regulates expression of Eph receptors and ephrins in mouse skin.

Vihanto, Meri M; Plock, Jan; Erni, Dominique; Frey, Brigitte M; Frey, Felix J; Huynh-Do, Uyen (2005). Hypoxia up-regulates expression of Eph receptors and ephrins in mouse skin. FASEB journal, 19(12), pp. 1689-1691. Federation of American Societies for Experimental Biology 10.1096/fj.04-3647fje

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Eph receptor tyrosine kinases and their ligands (ephrins) are key players during the development of the embryonic vasculature; however, their role and regulation in adult angiogenesis remain to be defined. Both receptors and ligands have been shown to be up-regulated in a variety of tumors. To address the hypothesis that hypoxia is an important regulator of Ephs/ephrins expression, we developed a mouse skin flap model of hypoxia. We demonstrate that our model truly represents segmental skin hypoxia by applying four independent methods: continuous measurement of partial cutaneous oxygen tension, monitoring of tissue lactate/pyruvate ratio, time course of hypoxia-inducible factor-1alpha (HIF-1alpha) induction, and localization of stabilized HIF-1alpha by immunofluorescence in the hypoxic skin flap. Our experiments indicate that hypoxia up-regulates not only HIF-1alpha and vascular endothelial growth factor (VEGF) expression, but also Ephs and ephrins of both A and B subclasses in the skin. In addition, we show that in Hep3B and PC-3 cells, the hypoxia-induced up-regulation of Ephs and ephrins is abrogated by small interfering RNA-mediated down-regulation of HIF-1alpha. These novel findings shed light on the role of this versatile receptor/ligand family in adult angiogenesis. Furthermore, our model offers considerable potential for analyzing distinct mechanisms of neovascularization in gene-targeted mice.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Huynh-Do, Uyen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Uyen Huynh-Do

Date Deposited:

17 Jun 2015 08:59

Last Modified:

17 Jun 2015 08:59

Publisher DOI:

10.1096/fj.04-3647fje

PubMed ID:

16081502

BORIS DOI:

10.7892/boris.69618

URI:

https://boris.unibe.ch/id/eprint/69618

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