title: Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation.
abstract: Several experimental data report both mitogenic and antimitogenic effects of bradykinin (BK). To conciliate these apparent opposite effects, we hypothesized that, depending on cell context activation, BK could reduce the mitogenic effect of growth factors. Therefore, in the present study we assessed the existence of possible negative cross talk between BK and potential pathogenic growth factors in freshly isolated rat glomeruli (IG). Next, we determined whether this cross talk could be pharmacologically recruited during angiotensin-converting enzyme (ACE) inhibition in the diabetic rat. In IG from normal rats, BK, via activation of the B(2) kinin receptor (B(2)R), causes a transient stimulation of ERK1/2 phosphorylation, whereas it inhibits ERK1/2 phosphorylation induced by IGF-1, PDGF-BB, VEGF, or basic FGF. The reduction of growth factor-induced ERK1/2 phosphorylation is abolished by an inhibitor of tyrosine phosphatase. In glomeruli from diabetic rats, hyperglycemia increased the phosphorylation level of ERK-1/2 as well as oxidative stress. The reversal of these events by ACE inhibition is mediated via B(2)R activation. These observations are consistent with a potential therapeutic role of BK and B(2)R during glomerulosclerosis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U388, IFR 31, Institut Louis Bugnard, 31403 Toulouse Cedex 4, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Cellier
authors.forename: Marilyne
authors.initials: M
authors.lastname: Mage
authors.forename: Johan
authors.initials: J
authors.lastname: Duchêne
authors.forename: Christiane
authors.initials: C
authors.lastname: Pécher
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Girolami
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D017526:Receptor, IGF Type 1 / Q000502:physiology; D018002:Receptors, Bradykinin / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology
chemical_list: D006133:Growth Substances; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D017978:Receptors, Growth Factor; D009569:Nitric Oxide; D017526:Receptor, IGF Type 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D001920:Bradykinin