title: Endoglin regulates mural cell adhesion in the circulatory system.
abstract: The circulatory system is walled off by different cell types, including vascular mural cells and podocytes. The interaction and interplay between endothelial cells (ECs) and mural cells, such as vascular smooth muscle cells or pericytes, play a pivotal role in vascular biology. Endoglin is an RGD-containing counter-receptor for β1 integrins and is highly expressed by ECs during angiogenesis. We find that the adhesion between vascular ECs and mural cells is enhanced by integrin activators and inhibited upon suppression of membrane endoglin or β1-integrin, as well as by addition of soluble endoglin (SolEng), anti-integrin α5β1 antibody or an RGD peptide. Analysis of different endoglin mutants, allowed the mapping of the endoglin RGD motif as involved in the adhesion process. In Eng (+/-) mice, a model for hereditary hemorrhagic telangectasia type 1, endoglin haploinsufficiency induces a pericyte-dependent increase in vascular permeability. Also, transgenic mice overexpressing SolEng, an animal model for preeclampsia, show podocyturia, suggesting that SolEng is responsible for podocytes detachment from glomerular capillaries. These results suggest a critical role for endoglin in integrin-mediated adhesion of mural cells and provide a better understanding on the mechanisms of vessel maturation in normal physiology as well as in pathologies such as preeclampsia or hereditary hemorrhagic telangiectasia.
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), c/Ramiro de Maeztu 9, 28040, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain.|Paris Descartes University, Sorbonne Paris Cite, Paris, France.|Hematology Department, AP-HP, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rossi
authors.affiliation: Hematology Department, AP-HP, Hôpital Européen Georges Pompidou, Paris, France.|Faculté de Pharmacie, Inserm UMR-S1140, Paris, France.
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.affiliation: Department of Surgery, Harvard Medical School, Children's Hospital, Boston, MA, 02115, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscolo
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), c/Ramiro de Maeztu 9, 28040, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Langa
authors.affiliation: Departamento de Anatomía e Histología Humanas, Facultad de Medicina, Universidad de Salamanca, 37007, Salamanca, Spain.|Instituto de Investigaciones Biomédicas de Salamanca (IBSAL), 37007, Salamanca, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Arevalo
authors.affiliation: Instituto de Investigaciones Biomédicas de Salamanca (IBSAL), 37007, Salamanca, Spain.|Departamento de Fisiología y Farmacología, Unidad de Fisiopatología Renal y Cardiovascular, Universidad de Salamanca, 37007, Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pericacho
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), c/Ramiro de Maeztu 9, 28040, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain.|Departamento de Fisiología y Farmacología, Unidad de Fisiopatología Renal y Cardiovascular, Universidad de Salamanca, 37007, Salamanca, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Gamella-Pozuelo
authors.affiliation: Inserm UMR-S1176, Le Kremlin Bicêtre, Paris, France.|Université Paris Sud, Le Kremlin Bicêtre, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kauskot
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), c/Ramiro de Maeztu 9, 28040, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Botella
authors.affiliation: Hematology Department, AP-HP, Hôpital Européen Georges Pompidou, Paris, France.|Faculté de Pharmacie, Inserm UMR-S1140, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.affiliation: Department of Surgery, Harvard Medical School, Children's Hospital, Boston, MA, 02115, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
authors.affiliation: Instituto de Investigaciones Biomédicas de Salamanca (IBSAL), 37007, Salamanca, Spain.|Departamento de Fisiología y Farmacología, Unidad de Fisiopatología Renal y Cardiovascular, Universidad de Salamanca, 37007, Salamanca, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Lopez-Novoa
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), c/Ramiro de Maeztu 9, 28040, Madrid, Spain. bernabeu.c@cib.csic.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain. bernabeu.c@cib.csic.es.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabeu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000473:pathology; D011247:Pregnancy; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics / Q000473:pathology
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019012:Integrin beta1; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface
keywords: Blood vessels; Cell adhesion; HHT; Kidney; TGF-β; Tubulogenesis