Genetic inactivation of Semaphorin 3C protects mice from acute kidney injury
| Autor: | Anxiang Cai, Guanyu Ye, Sandrine Placier, Perrine Frère, Brigitte Surin, Sophie Vandermeersch, Raphael Kormann, Yi-Chun Xu-Dubois, Magali Genest, Morgane Lannoy, Christos E. Chadjichristos, Jean-Claude Dussaule, Peter J. Scambler, Christos Chatziantoniou, Amélie Calmont |
|---|---|
| Přispěvatelé: | 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), UCL Great Ormond Street Institute of Child Health [London, UK], calmont, amelie |
| Rok vydání: | 2022 |
| Předmět: |
Male
urogenital system [SDV]Life Sciences [q-bio] Endothelial Cells Semaphorins Kidney class 3 semaphorin VEGF neuropilin 1 Capillary Permeability [SDV] Life Sciences [q-bio] Mice acute kidney injury Nephrology Reperfusion Injury Animals Humans Female genetically altered and transgenic models vascular permeability |
| Zdroj: | Kidney International Kidney International, 2022, 101 (4), pp.720-732. ⟨10.1016/j.kint.2021.12.028⟩ |
| ISSN: | 0085-2538 1523-1755 |
| Popis: | International audience; To guide the development of therapeutic interventions for acute kidney injury, elucidating the deleterious pathways of this global health problem is highly warranted. Emerging evidence has indicated a pivotal role of endothelial dysfunction in the etiology of this disease. We found that the class III semaphorin SEMA3C was ectopically upregulated with full length protein excreted into the blood and truncated protein secreted into the urine upon kidney injury and hypothesized a role for SEAM3C in acute kidney injury. Sema3c was genetically abrogated during acute kidney injury and subsequent kidney morphological and functional defects in two well-characterized models of acute kidney injury; warm ischemia/reperfusion and folic acid injection were analyzed. Employing a beta actin-dependent, inducible knockout of Sema3c, we demonstrate that in acute kidney injury SEMA3C promotes interstitial edema, leucocyte infiltration and tubular injury. Additionally, intravital microscopy combined with Evans Blue dye extravasation and primary culture of magnetically sorted peritubular endothelial cells identified a novel role for SEMA3C in promoting vascular permeability. Thus, our study points to microvascular permeability as an important driver of injury in acute kidney injury, and to SEMA3C as a novel permeability factor and potential target for therapeutic intervention. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|