title: CD154 Induces Matrix Metalloproteinase-9 Secretion in Human Podocytes.
abstract: Matrix remodeling is a key feature of glomerulosclerosis secondary to diabetes or hypertension. Podocytes contribute to glomerular basement membrane (GBM) turnover by producing matrix components and matrix remodelling enzymes, including matrix metalloproteinases (MMPs). The CD40/CD154 signaling pathway modulates matrix remodeling through the synthesis of MMPs and tissue inhibitors of MMPs. Platelets are a primary blood reservoir of CD154. Here we studied, the impact of the CD154/CD40 pathway on MMP-9 expression by cultured human podocytes. The role of CD40/CD154 was evaluated upon exposure of podocytes to recombinant human CD154 (rhCD154) or activated platelet supernatants from healthy human subjects. We first showed by protein and mRNA expression that CD40 was synthesized by podocytes and detectable on kidney tissue sections. CD40 expression was acquired during podocyte differentiation and enhanced upon exposure to rhCD154. In podocytes, rhCD154 induced an increase of MMP-9 production as shown by RT-PCR, Western blot and and gelatin zymography. Activated platelet supernatants induced MMP-9 mRNA synthesis in podocytes, an effect reduced by anti-CD40 antibody. Our results underscore a potential role for platelets through the CD40/CD154 signaling pathway in the control of GBM synthesis and degradation, via its regulatory role on MMP-9 production. CD154 secretion by activated platelets may contribute to GBM alterations in proteinuric nephropathies. J. Cell. Biochem. 117: 2737-2747, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France. claire.rigothier@chu-bordeaux.fr.|Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, F-33076 Bordeaux, France. claire.rigothier@chu-bordeaux.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Rigothier
authors.affiliation: INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Daculsi
authors.affiliation: INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lepreux
authors.affiliation: INSERM U1029, Université de Bordeaux, F-33405 Pessac, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Auguste
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation, 08003 Barcelona, Spain.|Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, California 94720-3200.
authors.forename: Julien
authors.initials: J
authors.lastname: Villeneuve
authors.affiliation: INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.|Service d'Anesthésie-Réanimation II, Centre Hospitalier Universitaire de Bordeaux, F-33600 Pessac, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Dewitte
authors.affiliation: CNRS UMR 5293, Institut des Maladies Neurodégénératives, F-33076 Bordeaux, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Doudnikoff
authors.affiliation: Children's Renal Unit and Academic Renal Unit, University of Bristol, Bristol, United Kingdom.
authors.forename: Moin
authors.initials: M
authors.lastname: Saleem
authors.affiliation: INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Bourget
authors.affiliation: INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.|Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, F-33076 Bordeaux, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Combe
authors.affiliation: INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Ripoche
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019013:CD40 Antigens; D012333:RNA, Messenger; D023201:CD40 Ligand; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: CD154; CD40; MMP9; PLATELETS; PODOCYTES