1. Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis
- Author
-
Denis Calise, Christine Delage, Jean-Philippe Pradère, Bénédicte Buffin-Meyer, Jean-Loup Bascands, Israel F. Charo, Julien Gonzalez, Sofia Mouttalib, Jean-José Maoret, Betty S. van der Veen, Joost-Peter Schanstra, Peter Heeringa, Julie Klein, Johan Duchene, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Zootechny Department of Experimental Micro-Surgery, Toulouse, CHU Toulouse [Toulouse], Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Pathology and Medical Biology, University Medical Center Groningen [Groningen] (UMCG), Gladstone Institute of Cardiovascular Disease, Department of Medicine, University of California [San Francisco] (UCSF), University of California-University of California-Cardiovascular Research Institute, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse]-Hôpital de Rangueil, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Simon, Marie Francoise, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-Cardiovascular Research Institute, Groningen Kidney Center (GKC), and Translational Immunology Groningen (TRIGR)
- Subjects
Male ,Chemokine ,Kidney Disease ,Time Factors ,T-Lymphocytes ,FIBROBLAST COLLAGEN ,030204 cardiovascular system & hematology ,Medical Biochemistry and Metabolomics ,Inbred C57BL ,Kidney ,PLASMINOGEN-ACTIVATOR INHIBITOR-1 ,Biochemistry ,T-Lymphocytes, Regulatory ,Mice ,0302 clinical medicine ,Fibrosis ,Pulmonary fibrosis ,Chemokine CCL7 ,Mice, Knockout ,0303 health sciences ,biology ,MONOCYTE CHEMOATTRACTANT PROTEIN-1 ,Regulatory ,3. Good health ,medicine.anatomical_structure ,Kidney Tubules ,Collagen ,medicine.symptom ,OBSTRUCTIVE NEPHROPATHY ,INTERSTITIAL FIBROSIS ,EXPRESSION ,medicine.medical_specialty ,Biochemistry & Molecular Biology ,endocrine system ,Knockout ,BONE-MARROW ,Biophysics ,Renal and urogenital ,Inflammation ,CCL7 ,Article ,Cell Line ,03 medical and health sciences ,Medicinal and Biomolecular Chemistry ,CHEMOTACTIC PROTEIN-3 ,Internal medicine ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,REGULATORY T-CELLS ,Molecular Biology ,Monocyte extravasation ,030304 developmental biology ,Animal ,PULMONARY-FIBROSIS ,Cell Biology ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,Immunology ,Disease Models ,Tubulointerstitial fibrosis ,biology.protein ,Biochemistry and Cell Biology - Abstract
Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can also have a beneficial anti-fibrotic role depending in particular on the stage of the pathology. Chemokines play an important role in monocyte extravasation in the inflammatory process. CCL2 has already been shown to be involved in the development of TIF but CCL7, a close relative of CCL2 and able to bind to similar receptors, has not been studied in renal disease. We therefore studied chemokine CCL7 in a model of unilateral ureteral obstruction (UUO)-induced TIF. We observed that the role of CCL7 differs depending on the stage of the pathology. In early stages (0-8 days), CCL7 deficient (CCL7-KO) mice displayed attenuated TIF potentially involving two mechanisms: an early (0-3 days) decrease of inflammatory cell infiltration followed (3-8 days) by a decrease in tubular ECM production independent of inflammation. In contrast, during later stages of obstruction (10-14 days), CCL7-KO mice displayed increased TIF which was again associated with reduced inflammation. Interestingly, the switch between this anti- to profibrotic effect was accompanied by an increased influx of immunosuppressive regulatory T cells. In conclusion, these results highlight for the first time a dual role for CCL7 in the development of renal TIF, deleterious in early stages but beneficial during later stages. (C) 2013 Elsevier Inc. All rights reserved.
- Published
- 2013
- Full Text
- View/download PDF