REGULATION OF THE MOUSE GLOMERULAR FILTRATION BY THE INTEGRIN LINKED KINASE (ILK). ROLE OF THE VASODILATORY CGMP PATHWAY

JOSE LUIS CANO-PEÑALVER; MERCEDES GRIEGA MERINO; GEMMA OLMOS; PALOMA MARTÍN; M. ALICIA CORTÉS; SUSANA LOPEZ-ONGIL; DIEGO RODRIGUEZ-PUYOL; SERGIO DE FRUTOS

Paris

Congreso; 49th ERA-EDTA CONGRESS; 2012

EDTA

Introduction and Aims: The guanosine 3′,5′-cyclic monophosphate (cGMP)-dependent signalling pathway plays an important role in the glomerular filtration, since vessel dilation appears when NO activates soluble guanylyl cyclase (sGC) that produces cGMP, which activates cGMP-dependent protein kinases (PKG). In most renal chronical diseases, the extracellular matrix (ECM) altered composition decreases the cGMP system activity. We demonstrated (de Frutos S et al, JASN 2005) that altered ECM and its interaction with the integrin-linked kinase (ILK) regulates mesangial sGC. Here, we studied the role of ILK in the mice renal cGMP-dependent vasodilatory system and the consequent glomerular filtration. Methods: We used a conditional ILK-deleted mice model (conditional KO) where the cGMP pathway was pharmacologically activated by NO-donor Isosorbide Dinitrate treatment for 24 hours. We analyzed urine volumes, creatine clearance and changes in cortical cGMP-releated protein levels by western blot. Results: We observed a quite significant poliuria in the ILK-conditional KO mice compared with controls. In order to study the role of the cGMP signalling pathway, we observed enhanced poliuria and creatine clearance levels after NO treatment, pointing to an increased cGMP- dependent pathway activity. Indeed, we observed increased cortical sGC and PKG protein levels expression in ILK-conditional KO mice, even though the 24 hours NO-treatment produced tachyphylaxis in these proteins. Conclusions: We propose ILK as a major player in the glomerular physiology and pathology. The lack of ILK increased cGMP-dependent glomerular filtration since ILK seems to regulate sGC and PKG expression in the glomeruli.