Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction
| Autor: | Sophie Vandermeersch, Naïke Bigé, Pierre Ronco, Safa Benhassine, Christos Chatziantoniou, Chantal Jouanneau, Jean-Jacques Boffa, Jean-Claude Dussaule, Nasim Shweke |
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| Přispěvatelé: | RONCO, Pierre, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Institut National de la Santé et de la Recherche Médicale and Université Pierre et Marie Curie., Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A MESH: Signal Transduction Time Factors Apoptosis MESH: Rats Sprague-Dawley Kidney urologic and male genital diseases Peritubular capillaries Nephrectomy MESH: Mice Knockout Rats Sprague-Dawley Thrombospondin 1 Mice MESH: Transforming Growth Factor beta1 0302 clinical medicine Fibrosis MESH: Animals Renal stem cell Chemokine CCL2 MESH: Thrombospondin 1 Mice Knockout MESH: Collagen Type III 0303 health sciences Nephritis renal progression renal fibrosis MESH: Gene Expression Regulation 3. Good health medicine.anatomical_structure Nephrology 030220 oncology & carcinogenesis MESH: Fibrosis [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Kidney Diseases medicine.symptom Inflammation Mediators MESH: Nephritis Signal Transduction Ureteral Obstruction TGF-β medicine.medical_specialty MESH: Rats MESH: Inflammation Mediators Inflammation MESH: Atrophy Transforming Growth Factor beta1 03 medical and health sciences Internal medicine MESH: Cell Proliferation [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] medicine Renal fibrosis Animals MESH: Mice MESH: Chemokine CCL2 030304 developmental biology Cell Proliferation MESH: Capillaries MESH: Kidney Diseases business.industry MESH: Apoptosis MESH: Vascular Endothelial Growth Factor A MESH: Chronic Disease MESH: Time Factors Kidney metabolism MESH: Kidney medicine.disease MESH: Male Capillaries Rats MESH: Nephrectomy Disease Models Animal Endocrinology Collagen Type III Gene Expression Regulation Chronic Disease Atrophy MESH: Ureteral Obstruction MESH: Disease Models Animal business Kidney disease Transforming growth factor |
| Zdroj: | Kidney International Kidney International, 2012, 81 (12), pp.1226-38. ⟨10.1038/ki.2012.21⟩ Kidney International, Nature Publishing Group, 2012, 81 (12), pp.1226-38. ⟨10.1038/ki.2012.21⟩ |
| ISSN: | 0085-2538 1523-1755 |
| Popis: | International audience; Thrombospondin-1 (TSP-1) is an endogenous activator of transforming growth factor-β (TGF-β), and an anti-angiogenic factor, which may prevent kidney repair. Here we investigated whether TSP-1 is involved in the development of chronic kidney disease using rats with unilateral ureteral obstruction, a well-known model to study renal fibrosis. Obstruction of 10 days duration induced inflammation, tubular cell atrophy, dilation, apoptosis, and proliferation, leading to interstitial fibrosis. TSP-1 expression was increased in parallel to that of collagen III and TGF-β. Relief of the obstruction at day 10 produced a gradual improvement in renal structure and function, the reappearance of peritubular capillaries, and restoration of renal VEGF content over a 7- to 15-day post-relief period. TSP-1 expression decreased in parallel with that of TGF-β1 and collagen III. Mice in which the TSP-1 gene was knocked out displayed less inflammation and had better preservation of renal tissue and the peritubular capillary network compared to wild-type mice. Additional studies showed that the inflammatory effect of TSP-1 was mediated, at least in part, by monocyte chemoattractant protein-1 and activation of the Th17 pathway. Thus, TSP-1 is an important profibrotic and inflammatory mediator of renal disease. Blockade of its action may be a treatment against the development of chronic kidney disease. |
| Databáze: | OpenAIRE |
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