Notch3 orchestrates epithelial and inflammatory responses to promote acute kidney injury
| Autor: | Niki Prakoura, Zela Keuylian, Sandrine Placier, Christos Chatziantoniou, Jean-Claude Dussaule, Panagiotis Kavvadas, Aude Dorison, Christos E. Chadjichristos |
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| Přispěvatelé: | Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Chadjichristos, Christos |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Ischemia Inflammation 030204 cardiovascular system & hematology Epithelium Proinflammatory cytokine Epithelial Damage 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Humans epithelial damage Promoter Regions Genetic Receptor Notch3 Mice Knockout [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology business.industry Macrophages Acute kidney injury Notch3 NF-kappa B Epithelial Cells Acute Kidney Injury medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Kidney Tubules Nephrology inflammation Reperfusion Injury Knockout mouse Cancer research medicine.symptom business Reperfusion injury [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Kidney disease |
| Zdroj: | Kidney International Kidney International, Nature Publishing Group, 2018, 94 (1), pp.126-138. ⟨10.1016/j.kint.2018.01.031⟩ |
| ISSN: | 1523-1755 0085-2538 |
| DOI: | 10.1016/j.kint.2018.01.031⟩ |
| Popis: | International audience; Acute kidney injury is a major risk factor for subsequent chronic renal and/or cardiovascular complications. Previous studies have shown that Notch3 was de novo expressed in the injured renal epithelium in the early phases of chronic kidney disease. Here we examined whether Notch3 is involved in the inflammatory response and the epithelial cell damage that typifies ischemic kidneys using Notch3 knockout mice and mice with short-term activated Notch3 signaling (N3ICD) in renal epithelial cells. After ischemia/reperfusion, N3ICD mice showed exacerbated infiltration of inflammatory cells and severe tubular damage compared to control mice. Inversely, Notch3 knockout mice were protected against ischemia/reperfusion injury. Renal macrophages derived from Notch3 knockout mice failed to activate proinflammatory cytokines. Chromatin immunoprecipitation analysis of the Notch3 promoter identified NF-κB as the principal inducer of Notch3 in ischemia/reperfusion. Thus, Notch3 induced by NF-κB in the injured epithelium sustains a proinflammatory environment attracting activated macrophages to the site of injury leading to a rapid deterioration of renal function and structure. Hence, targeting Notch3 may provide a novel therapeutic strategy against ischemia/reperfusion and acute kidney injury by preservation of epithelial structure and disruption of proinflammatory signaling. |
| Databáze: | OpenAIRE |
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