Universität zu Köln

Zeilbeck, Ludwig F., Mueller, Birgit B., Leopold, Stephanie A., Senturk, Berna, Langmann, Thomas, Tamm, Ernst R. and Ohlmann, Andreas ORCID: 0000-0002-7101-9361 (2016). Norrin mediates angiogenic properties via the induction of insulin-like growth factor-1. Exp. Eye Res., 145. S. 317 - 327. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1096-0007

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Abstract

Norrin is an angiogenic signaling molecule that activates canonical Wnt/beta-catenin signaling, and is involved in capillary formation in retina and brain. Moreover, Norrin induces vascular repair following an oxygen-induced retinopathy (OIR), the model of retinopathy of prematurity in mice. Since insulin-like growth factor (IGF)-1 is a very potent angiogenic molecule, we investigated if IGF-1 is a downstream mediator of Norrin's angiogenic properties. In retinae of transgenic mice with an ocular overexpression of Norrin (beta B1-Norrin), we found at postnatal day (P)11 a significant increase of IGF-1 mRNA compared to wild-type littermates. In addition, after treatment of cultured Muller cells or dermal microvascular endothelial cells with Norrin we observed an increase of IGF-1 and its mRNA, an effect that could be blocked with DKK-1, an inhibitor of Wnt/beta-catenin signaling. When OIR was induced, the expression of IGF-1 was significantly suppressed in both transgenic beta B1-Norrin mice and wild-type littermates when compared to wild-type animals that were housed in room air. Furthermore, at P13, one day after the mice had returned to normoxic conditions, IGF-1 levels were significantly higher in transgenic mice compared to wild-type littermates. Finally, after intravitreal injections of inhibitory alpha-IGF-1 antibodies at P12 or at P12 and P14, the Norrin-mediated vascular repair was significantly attenuated. We conclude that Norrin induces the expression of IGF-1 via an activation of the Wnt/beta-catenin signaling pathway, an effect that significantly contributes to the protective effects of Norrin against an OIR. (C) 2015 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zeilbeck, Ludwig F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Birgit B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Leopold, Stephanie A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Senturk, Berna UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Tamm, Ernst R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ohlmann, Andreas UNSPECIFIED orcid.org/0000-0002-7101-9361 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-280404
DOI:	10.1016/j.exer.2015.12.001
Journal or Publication Title:	Exp. Eye Res.
Volume:	145
Page Range:	S. 317 - 327
Date:	2016
Publisher:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication:	LONDON
ISSN:	1096-0007
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OXYGEN-INDUCED RETINOPATHY; IGF-I; ENDOTHELIAL-CELLS; RETINAL NEOVASCULARIZATION; DIABETIC-RETINOPATHY; VASCULAR DEVELOPMENT; GENE-EXPRESSION; TRANSGENIC MICE; BETA-CATENIN; EYE DISEASE Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28040