B2 receptor activation reduces Erk1 and Erk2 phosphorylation induced by insulin-like growth factor-1, platelet-derived growth factor-BB, and high glucose in rat isolated glomeruli.
Several experimental data document an activation of the mitogen-activated protein kinases Erk1 and Erk2 by bradykinin (BK), an agonist of the kinin B2 receptor (B2R). In contrast, other reports showed an inhibitory modulation of mitogenesis by BK. Therefore, we explored in the isolated glomeruli the effect of B2R activation on the signaling of insulin-like growth factor-1 (IGF-1), platelet-derived growth factor-BB (PDGF-BB), and high glucose (HG), three factors that are believed to be involved in the development of glomerulosclerosis via the phosphorylation of Erk1 and Erk2. We observed that the activation of B2R negatively modulates the phosphorylation of Erk1 and Erk2 induced by IGF-1, PDGF-BB, and HG in the glomerulus. These effects are consistent with the hypothesis of a protective role for BK in the kidney during development of glomerulosclerosis and renal pathologies associated with a hyperproliferative state.
Cellier
Eric
E
INSERM U388, IFR 31, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
Duchêne
Johan
J
Pécher
Christiane
C
Alric
Céline
C
Bascands
Jean-Loup
JL
Schanstra
Joost Peter
JP
Girolami
Jean-Pierre
JP
D000818:Animals; D000077214:Becaplermin; D005947:Glucose / Q000494:pharmacology* / Q000502:physiology; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D000077214:Becaplermin; D007334:Insulin-Like Growth Factor I; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose