Delayed treatment with plasminogen activator inhibitor-1 decoys reduces tubulointerstitial fibrosis
| Autor: | Sharmila D. Chauhan, Rana Chaaya, Eric Neau, Caroline Nevoit, Jean-Loup Bascands, Julien Gonzalez, Joost P. Schanstra, Julie Klein, Denis Calise, Mathieu Miravete, Christine Delage, Bénédicte Buffin-Meyer |
|---|---|
| Přispěvatelé: | Simon, Marie Francoise, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
MESH: Hepatocyte Growth Factor Plasmin MESH: Fibrinolysin chemistry.chemical_compound Mice Fibrosis MESH: Tissue Plasminogen Activator Serpin E2 MESH: Fibronectins MESH: Animals Fibrinolysin MESH: Collagen Type III biology Hepatocyte Growth Factor MESH: Peptides Kidney Tubules Plasminogen activator inhibitor-1 Tissue Plasminogen Activator MESH: Fibrosis MESH: Kidney Tubules Hepatocyte growth factor Kidney Diseases medicine.drug Ureteral Obstruction Collagen Type IV General Biochemistry Genetics and Molecular Biology MESH: Urokinase-Type Plasminogen Activator MESH: Serpins medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice MESH: Collagen Type IV Serpins Urokinase MESH: Kidney Diseases Macrophages MESH: Macrophages medicine.disease Urokinase-Type Plasminogen Activator MESH: Male Fibronectins Fibronectin Collagen Type III chemistry Immunology Tubulointerstitial fibrosis biology.protein Cancer research MESH: Ureteral Obstruction Peptides Plasminogen activator |
| Zdroj: | Experimental biology and medicine (Maywood, N.J.) Experimental biology and medicine (Maywood, N.J.), 2009, 234 (12), pp.1511-8. ⟨10.3181/0903-RM-105⟩ |
| DOI: | 10.3181/0903-RM-105⟩ |
| Popis: | International audience; We examined the capacity of delayed inhibition of plasminogen activator inhibitor-1 (PAI-1) to reduce tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO) in mice. Small peptides mimicking parts of urokinase (uPA) and tissular plasminogen activator (tPA) and serving as decoy molecules for PAI-1 were administered daily during the late stages (3 to 8 days) of UUO. Treatment with PAI-1 decoys reduced interstitial deposition of fibronectin, collagen III and collagen IV without changes in macrophage and myofibroblast infiltration. Interestingly, while PAI-1 activity was reduced and the combined uPA and tPA activity was increased, the antifibrotic effect was obtained without modification of plasmin activity but with increased of hepatocyte growth factor (HGF) expression. We show for the first time that treatment with small PAI-1 decoy peptides reduces established tubulointerstitial fibrosis. This protective effect probably resulted from increased degradation of the extracellular matrix by an HGF dependent mechanism. |
| Databáze: | OpenAIRE |
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