CD154 Induces Matrix Metalloproteinase-9 Secretion in Human Podocytes.
J. Cell. Biochem.. 2016-05-05; 117(12): 2737-2747
DOI: 10.1002/jcb.25571
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1. J Cell Biochem. 2016 Dec;117(12):2737-2747. doi: 10.1002/jcb.25571. Epub 2016 May
5.
CD154 Induces Matrix Metalloproteinase-9 Secretion in Human Podocytes.
Rigothier C(1)(2), Daculsi R(3), Lepreux S(3), Auguste P(4), Villeneuve J(5)(6),
Dewitte A(3)(7), Doudnikoff E(8), Saleem M(9), Bourget C(3), Combe C(3)(10),
Ripoche J(3).
Author information:
(1)INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.
.
(2)Service de Néphrologie Transplantation Dialyse, Centre Hospitalier
Universitaire de Bordeaux, F-33076 Bordeaux, France.
.
(3)INSERM U1026, Université de Bordeaux, F-33076 Bordeaux, France.
(4)INSERM U1029, Université de Bordeaux, F-33405 Pessac, France.
(5)Cell and Developmental Biology Programme, Centre for Genomic Regulation, 08003
Barcelona, Spain.
(6)Department of Molecular and Cell Biology, Howard Hughes Medical Institute,
University of California, Berkeley, California 94720-3200.
(7)Service d’Anesthésie-Réanimation II, Centre Hospitalier Universitaire de
Bordeaux, F-33600 Pessac, France.
(8)CNRS UMR 5293, Institut des Maladies Neurodégénératives, F-33076 Bordeaux,
France.
(9)Children’s Renal Unit and Academic Renal Unit, University of Bristol, Bristol,
United Kingdom.
(10)Service de Néphrologie Transplantation Dialyse, Centre Hospitalier
Universitaire de Bordeaux, F-33076 Bordeaux, France.
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.
© 2016 Wiley Periodicals, Inc.
DOI: 10.1002/jcb.25571
PMID: 27070919 [Indexed for MEDLINE]