Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice
| Autor: | Alexandrine Foucault-Bertaud, Richard Bachelier, Panagiotis Kavvadas, Maja T. Lindenmeyer, Ahmad Joshkon, Nathalie Bardin, Ahmed Abed, Noémie Jourde-Chiche, Clemens D. Cohen, Christos E. Chadjichristos, Florence Authier, Françoise Dignat-George, Stéphane Burtey, Magali Genest, Aurélie S. Leroyer, Marcel Blot-Chabaud |
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| Přispěvatelé: | Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Contextes, Variation, Usages : Groupe de Recherche en linguistique des langues germaniques et scandinaves de Paris-Sorbonne (CoVariUs), Université Paris-Sorbonne (UP4), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-11-BSV1-0019,READ,CD146 et JAMs dans le contrôle de l'intégrité des junctions endothéliales : des bases moléculaires aux maladies inflammatoires rénales.(2011), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians University [Munich] (LMU), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Chadjichristos, Christos, Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ludwig Maximilian University [Munich] (LMU), Leroyer, Aurelie |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
mice [SDV]Life Sciences [q-bio] Kidney Glomerulus Inflammation CD146 Antigen 030204 cardiovascular system & hematology urologic and male genital diseases Experimental glomerulonephritis [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology Gene Knockout Techniques 03 medical and health sciences Glomerulonephritis 0302 clinical medicine Fibrosis Drug Discovery Internal Medicine Animals Medicine Proteinuria business.industry Monocyte fibrosis Endothelial Cells medicine.disease [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology Up-Regulation [SDV] Life Sciences [q-bio] Disease Models Animal Intercellular Junctions 030104 developmental biology medicine.anatomical_structure inflammation Immunology monocyte CD146 medicine.symptom proteinuria business |
| Zdroj: | Hypertension Hypertension, American Heart Association, 2021, 77 (4), pp.1260-1272. ⟨10.1161/HYPERTENSIONAHA.119.14176⟩ Hypertension, 2021, 77 (4), pp.1260-1272. ⟨10.1161/HYPERTENSIONAHA.119.14176⟩ |
| ISSN: | 0194-911X 1524-4563 |
| Popis: | International audience; CD146 is an endothelial junctional adhesion molecule, which expression is increased in human glomerular diseases. However, the pathological significance of this overexpression remains unknown. Induction of glomerulonephritis in mice, by using nephrotoxic serum, showed that CD146 expression was highly induced within damaged glomeruli and was associated with renal inflammation and fibrosis. Interestingly, 2 weeks after glomerulonephritis induction, CD146 knockout mice showed preserved renal function as proteinuria and blood urea nitrogen levels were significantly lower compared with wild-type littermates. Furthermore, renal structure was considerably conserved, since crescents formation, tubular dilation, monocyte and lymphocyte infiltration, and interstitial renal fibrosis were highly reduced. Colocalization with markers for different types of glomerular cells showed that CD146 expression was mainly increased within the injured endothelium of the glomerular tuft. Consequently, we generated a new transgenic strain in which CD146 was specifically deleted in the vascular endothelium. Similarly to CD146 knockout, these mice showed preservation of renal structure and function after the induction of glomerulonephritis compared with wild-type animals. These data show that endothelial CD146 plays a major role in glomerulonephritis and may represent a novel therapeutic target to reduce glomerular damage and the progression of renal disease. |
| Databáze: | OpenAIRE |
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