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Niaudet, Colin
Publications (6 of 6) Show all publications
Laviña, B., Castro, M., Niaudet, C., Cruys, B., Álvarez-Aznar, A., Carmeliet, P., . . . Gängel, K. (2018). Defective endothelial cell migration in the absence of Cdc42 leads to capillary-venous malformations. Development, 145(13), Article ID UNSP dev161182.
Open this publication in new window or tab >>Defective endothelial cell migration in the absence of Cdc42 leads to capillary-venous malformations
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2018 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 145, no 13, article id UNSP dev161182Article in journal (Refereed) Published
Abstract [en]

Formation and homeostasis of the vascular system requires several coordinated cellular functions, but their precise interplay during development and their relative importance for vascular pathologies remain poorly understood. Here, we investigated the endothelial functions regulated by Cdc42 and their in vivo relevance during angiogenic sprouting and vascular morphogenesis in the postnatal mouse retina. We found that Cdc42 is required for endothelial tip cell selection, directed cell migration and filopodia formation, but dispensable for cell proliferation or apoptosis. Although the loss of Cdc42 seems generally compatible with apical-basal polarization and lumen formation in retinal blood vessels, it leads to defective endothelial axial polarization and to the formation of severe vascular malformations in capillaries and veins. Tracking of Cdc42-depleted endothelial cells in mosaic retinas suggests that these capillary-venous malformations arise as a consequence of defective cell migration, when endothelial cells that proliferate at normal rates are unable to re-distribute within the vascular network.

Keywords
Vascular malformations, Cdc42, Cell migration, Endothelial axial polarity, Angiogenesis, Proliferation
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-361537 (URN)10.1242/dev.161182 (DOI)000439224400008 ()29853619 (PubMedID)
Funder
Swedish Research Council, VR2015-00550EU, European Research Council, 2011-294556EU, European Research Council, EU-ERC269073Knut and Alice Wallenberg Foundation, 2012.0272EU, FP7, Seventh Framework Programme, 317250Swedish Cancer Society, CAN2015/771The Wenner-Gren Foundation
Available from: 2018-10-01 Created: 2018-10-01 Last updated: 2018-10-01Bibliographically approved
Egaña, I., Kaito, H., Nitzsche, A., Becker, L., Ballester-Lopez, C., Niaudet, C., . . . Hellström, M. (2017). Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema. Scientific Reports, 7(15453)
Open this publication in new window or tab >>Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 15453Article in journal (Refereed) Published
Abstract [en]

Paladin (Pald1, mKIAA1274 or x99384) was identified in screens for vascular-specific genes and is a putative phosphatase. Paladin has also been proposed to be involved in various biological processes such as insulin signaling, innate immunity and neural crest migration. To determine the role of paladin we have now characterized the Pald1 knock-out mouse in a broad array of behavioral, physiological and biochemical tests. Here, we show that female, but not male, Pald1 heterozygous and homozygous knock-out mice display an emphysema-like histology with increased alveolar air spaces and impaired lung function with an obstructive phenotype. In contrast to many other tissues where Pald1 is restricted to the vascular compartment, Pald1 is expressed in both the epithelial and mesenchymal compartments of the postnatal lung. However, in Pald1 knock-out females, there is a specific increase in apoptosis and proliferation of endothelial cells, but not in non-endothelial cells. This results in a transient reduction of endothelial cells in the maturing lung. Our data suggests that Pald1 is required during lung vascular development and for normal function of the developing and adult lung in a sex-specific manner. To our knowledge, this is the first report of a sex-specific effect on endothelial cell apoptosis.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-281704 (URN)10.1038/s41598-017-14894-9 (DOI)000415023200014 ()29133847 (PubMedID)
Funder
Swedish Cancer SocietyÅke Wiberg Foundation
Note

List of authors in thesis manuscript: Egaña I, Nitzsche A, Kaito H, Becker L, Garrett L, Niaudet C, Liu W, Vanlandewijck M, Larsson J, Hrabe de Angelis M, Fuchs H, Gailus-Durner V, Vernaleken A, Klopstock T, Hölter S M, Wurst W, Rask-Andersen H, German Mouse Clinic Consortium, Yildirim A Ö, Hellström M

Available from: 2016-04-18 Created: 2016-03-29 Last updated: 2018-02-22Bibliographically approved
Niaudet, C., Bonnaud, S., Guillonneau, M., Gouard, S., Gaugler, M.-H., Dutoit, S., . . . Paris, F. (2017). Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38 MAPK pathways in endothelial cells apoptosis. Cellular Signalling, 33, 10-21
Open this publication in new window or tab >>Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38 MAPK pathways in endothelial cells apoptosis
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2017 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 33, p. 10-21Article in journal (Refereed) Published
Abstract [en]

The p38 MAPK signaling pathway is essential in the cellular response to stress stimuli, in particular in the endothelial cells that are major target of external stress. The importance of the bioactive sphingolipid ceramide generated by acid sphingomyelinase is also firmly established in stress-induced endothelial apoptotic cell death. Despite a suggested link between the p38 MAPK and ceramide pathways, the exact molecular events of this connection remain elusive. In the present study, by using two different activators of p38 MAPK, namely anisomycin and ionizing radiation, we depicted how ceramide generated by acid sphingomyelinase was involved in p38 MAPK-dependent apoptosis of endothelial cells. We first proved that both anisomycin and ionizing radiation conducted to apoptosis through activation of p38 MAPK in human microvascular endothelial cells HMEC-1. We then found that both treatments induced activation of acid sphingomyelinase and the generation of ceramide. This step was required for p38 MAPK activation and apoptosis. We finally showed that irradiation, as well as treatment with exogenous C-16-ceramide or bacterial sphingomyelinase, induced in endothelial cells a deep reorganization of the plasma membrane with formation of large lipid platforms at the cell surface, leading to p38 MAPK activation ' and apoptosis in endothelial cells. Altogether, our results proved that the plasma membrane reorganization leading to ceramide production is essential for stress-induced activation of p38 MAPK and apoptosis in endothelial cells and established the link between the acid sphingomyelinase/ceramide and p38 MAPK pathways.

Keywords
Endothelium, Stress signaling, Membrane remodeling, Ceramide p38 MAPK, Apoptosis
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-321169 (URN)10.1016/j.cellsig.2017.02.001 (DOI)000397683500002 ()28179144 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 326512
Available from: 2017-05-12 Created: 2017-05-12 Last updated: 2018-01-13Bibliographically approved
Musa, G., Engel, F. B. & Niaudet, C. (2016). Heart development, angiogenesis, and blood-brain barrier function is modulated by adhesion GPCRs. In: Tobias Langenhan, Torsten Schöneberg (Ed.), Adhesion G Protein-coupled Receptors: Molecular, Physiological and Pharmacological Principles in Health and Disease (pp. 351-368). Springer Publishing Company
Open this publication in new window or tab >>Heart development, angiogenesis, and blood-brain barrier function is modulated by adhesion GPCRs
2016 (English)In: Adhesion G Protein-coupled Receptors: Molecular, Physiological and Pharmacological Principles in Health and Disease / [ed] Tobias Langenhan, Torsten Schöneberg, Springer Publishing Company, 2016, p. 351-368Chapter in book (Refereed)
Abstract [en]

The cardiovascular system in adult organisms forms a network of interconnected endothelial cells, supported by mural cells and displaying a high degree of hierarchy: arteries emerging from the heart ramify into arterioles and then capillaries, which return to the venous systems through venules and veins. The cardiovascular system allows blood circulation, which in turn is essential for hemostasis through gas diffusion, nutrient distribution, and cell trafficking. In this chapter, we have summarized the current knowledge on how adhesion GPCRs (aGPCRs) impact heart development, followed by their role in modulating vascular angiogenesis.

Place, publisher, year, edition, pages
Springer Publishing Company, 2016
Series
Handbook of Experimental Pharmacology ; 234
Keywords
Adhesion GPCRs, Angiogenesis, Blood-brain-barrier, Cardiovascular, Endothelium, Heart development, Trabeculation
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-310242 (URN)10.1007/978-3-319-41523-9_16 (DOI)2-s2.0-84995495611 (Scopus ID)978-3-319-41523-9 (ISBN)978-3-319-41521-5 (ISBN)
Available from: 2017-01-03 Created: 2016-12-13 Last updated: 2018-01-13Bibliographically approved
Niaudet, C., Hofmann, J. J., Mae, M. A., Jung, B., Gängel, K., Vanlandewijck, M., . . . Betsholtz, C. (2015). Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium. PLoS ONE, 10(9), Article ID e0137949.
Open this publication in new window or tab >>Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0137949Article in journal (Refereed) Published
Abstract [en]

Despite its known expression in both the vascular endothelium and the lung epithelium, until recently the physiological role of the adhesion receptor Gpr116/ADGRF5 has remained elusive. We generated a new mouse model of constitutive Gpr116 inactivation, with a large genetic deletion encompassing exon 4 to exon 21 of the Gpr116 gene. This model allowed us to confirm recent results defining Gpr116 as necessary regulator of surfactant homeostasis. The loss of Gpr116 provokes an early accumulation of surfactant in the lungs, followed by a massive infiltration of macrophages, and eventually progresses into an emphysemalike pathology. Further analysis of this knockout model revealed cerebral vascular leakage, beginning at around 1.5 months of age. Additionally, endothelial-specific deletion of Gpr116 resulted in a significant increase of the brain vascular leakage. Mice devoid of Gpr116 developed an anatomically normal and largely functional vascular network, surprisingly exhibited an attenuated pathological retinal vascular response in a model of oxygen-induced retinopathy. These data suggest that Gpr116 modulates endothelial properties, a previously unappreciated function despite the pan-vascular expression of this receptor. Our results support the key pulmonary function of Gpr116 and describe a new role in the central nervous system vasculature.

National Category
Immunology in the medical area Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-265915 (URN)10.1371/journal.pone.0137949 (DOI)000361792100023 ()26394398 (PubMedID)
Funder
EU, European Research Council, 294556EU, European Research Council, ITN-2012-317250-VESSELSwedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2015-11-04 Created: 2015-11-04 Last updated: 2018-04-07
Laviña, B., Castro, M., Niaudet, C., Bert, C., Peter, C., Bentley, K., . . . Gängel, K.Defective endothelial cell migration in the absence of Cdc42 leads to capillary-venous malformations: Cdc42 and vascular malformations.
Open this publication in new window or tab >>Defective endothelial cell migration in the absence of Cdc42 leads to capillary-venous malformations: Cdc42 and vascular malformations
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(English)Manuscript (preprint) (Other academic)
Keywords
Vascular malformations, Cdc42, cell migration, planar-cell-polarity, angiogenesis, proliferation
National Category
Cell Biology
Identifiers
urn:nbn:se:uu:diva-347774 (URN)
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-10-01Bibliographically approved
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