Furin deficiency in myeloid cells leads to attenuated revascularization in a mouse-model of oxygen-induced retinopathy.

Autor: Vähätupa M; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland., Cordova ZM; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland; Immunoregulation, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland., Barker H; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland., Aittomäki S; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland; Immunoregulation, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland., Uusitalo H; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland; Eye Centre, Tampere University Hospital, Tampere, Finland., Järvinen TAH; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland; Departments of Musculoskeletal Disorders, Tampere University Hospital, Tampere, Finland., Pesu M; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland; Immunoregulation, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland; Departments of Dermatology, Tampere University Hospital, Tampere, Finland., Uusitalo-Järvinen H; Faculty of Medicine & Life Sciences, University of Tampere, Tampere, Finland; Eye Centre, Tampere University Hospital, Tampere, Finland. Electronic address: llhauus@uta.fi.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2018 Jan; Vol. 166, pp. 160-167. Date of Electronic Publication: 2017 Oct 13.
DOI: 10.1016/j.exer.2017.10.013
Abstrakt: Ischemic retinopathy is a vision-threatening disease associated with chronic retinal inflammation and hypoxia leading to abnormal angiogenesis. Furin, a member of the proprotein convertase family of proteins, has been implicated in the regulation of angiogenesis due to its essential role in the activation of several angiogenic growth factors, including vascular endothelial growth factor-C (VEGF-C), VEGF-D and transforming growth factor - β (TGF- β). In the present study, we evaluated expression of furin in the retina and its role in retinal angiogenesis. As both inflammation and hypoxia contribute to angiogenesis, the role of furin was evaluated using myeloid-cell specific furin knockout (KO) mice (designated LysMCre-fur (fl/fl) ) both in developmental retinal angiogenesis as well as in hypoxia-driven angiogenesis using the oxygen-induced retinopathy (OIR) model. In the retina, furin expression was detected in endothelial cells, macrophages and, to some extent, in neurons. The rate of angiogenesis was not different in LysMCre-fur (fl/fl) mice when compared to their wild-type littermates during development. In the OIR model, the revascularization of retina was significantly delayed in LysMCre-fur (fl/fl) mice compared to their wild-type littermates, while there was no compensatory increase in the preretinal neovascularization in LysMCre-fur (fl/fl) mice. These results demonstrate that furin expression in myeloid cells plays a significant role in hypoxia-induced angiogenesis in retina.
(Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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