caa a22 4500 606175172 CHVBK 20210128100741.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00018-015-1972-5 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1972-5 Protease nexin-1 regulates retinal vascular development [Elektronische Daten] [Sonia Selbonne, Deborah Francois, William Raoul, Yacine Boulaftali, Florian Sennlaub, Martine Jandrot-Perrus, Marie-Christine Bouton, Véronique Arocas] We recently identified protease nexin-1 (PN-1) or serpinE2, as a possibly underestimated player in maintaining angiogenic balance. Here, we used the well-characterized postnatal vascular development of newborn mouse retina to further investigate the role and the mechanism of action of PN-1 in physiological angiogenesis. The development of retinal vasculature was analysed by endothelial cell staining with isolectin B4. PN-1-deficient (PN-1−/−) retina displayed increased vascularization in the postnatal period, with elevated capillary thickness and density, compared to their wild-type littermate (WT). Moreover, PN-1−/− retina presented more veins/arteries than WT retina. The kinetics of retinal vasculature development, retinal VEGF expression and overall retinal structure were similar in WT and PN-1−/− mice, but we observed a hyperproliferation of vascular cells in PN-1−/− retina. Expression of PN-1 was analysed by immunoblotting and X-Gal staining of retinas from mice expressing beta-galactosidase under a PN-1 promoter. PN-1 was highly expressed in the first week following birth and then progressively decreased to a low level in adult retina where it localized on the retinal arteries. PCR arrays performed on mouse retinal RNA identified two angiogenesis-related factors, midkine and Smad5, that were overexpressed in PN-1−/− newborn mice and this was confirmed by RT-PCR. Both the higher vascularization and the overexpression of midkine and Smad5 mRNA were also observed in gastrocnemius muscle of PN-1−/− mice, suggesting that PN-1 interferes with these pathways. Together, our results demonstrate that PN-1 strongly limits physiological angiogenesis and suggest that modulation of PN-1 expression could represent a new way to regulate angiogenesis. Springer Basel, 2015 Serpin nationallicence Angiogenesis nationallicence Retina nationallicence SerpinE2 nationallicence PN-1 nationallicence Selbonne Sonia LVTS, INSERM, U1148, Paris, France aut Francois Deborah LVTS, INSERM, U1148, Paris, France aut Raoul William UMR_S 968, Institut de la Vision, Paris, France aut Boulaftali Yacine LVTS, INSERM, U1148, Paris, France aut Sennlaub Florian UMR_S 968, Institut de la Vision, Paris, France aut Jandrot-Perrus Martine LVTS, INSERM, U1148, Paris, France aut Bouton Marie-Christine LVTS, INSERM, U1148, Paris, France aut Arocas Véronique LVTS, INSERM, U1148, Paris, France aut Cellular and Molecular Life Sciences Springer Basel 72/20(2015-10-01), 3999-4011 1420-682X 72:20<3999 2015 72 18 https://doi.org/10.1007/s00018-015-1972-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1972-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Selbonne Sonia LVTS, INSERM, U1148, Paris, France aut NATIONALLICENCE 700 1- Francois Deborah LVTS, INSERM, U1148, Paris, France aut NATIONALLICENCE 700 1- Raoul William UMR_S 968, Institut de la Vision, Paris, France aut NATIONALLICENCE 700 1- Boulaftali Yacine LVTS, INSERM, U1148, Paris, France aut NATIONALLICENCE 700 1- Sennlaub Florian UMR_S 968, Institut de la Vision, Paris, France aut NATIONALLICENCE 700 1- Jandrot-Perrus Martine LVTS, INSERM, U1148, Paris, France aut NATIONALLICENCE 700 1- Bouton Marie-Christine LVTS, INSERM, U1148, Paris, France aut NATIONALLICENCE 700 1- Arocas Véronique LVTS, INSERM, U1148, Paris, France aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/20(2015-10-01), 3999-4011 1420-682X 72:20<3999 2015 72 18