title: Rho kinase inhibition in diabetic nephropathy.
abstract: OBJECTIVE
  The Rho GTPases and their downstream effectors Rho-associated kinases (ROCKs) appear to be the molecules that converge numerous pathophysiological signals triggered by the diabetic milieu and represent promising molecular targets for nephroprotective treatment in diabetes. The review discusses recent studies exploring the consequences of diabetes-induced Rho-ROCK activation in the kidney and the effects of ROCK inhibition (ROCKi) in experimental diabetic nephropathy.
  
  
  RESULTS
  Recent studies in models of type 1 and type 2 diabetes have indicated blood-pressure-independent nephroprotective actions of ROCKi in diabetic nephropathy. The underlying mechanisms include attenuation of diabetes-induced increases in renal expression of prosclerotic cytokines and extracellular matrix, resulting in slower development of glomerulosclerosis and interstitial fibrosis. The studies have also shown antiproteinuric affects of ROCKi that could be related to reductions in permeability of glomerular barrier and beneficial effects on podocytes. Moreover hemodynamic mechanisms might be also involved.
  
  
  CONCLUSIONS
  Despite remaining questions in this field, such as the specificity of currently available ROCKi, or the roles of individual ROCK isoforms, recent evidence in experimental diabetes, together with evidence generated in models of nondiabetic kidney disease and in clinical studies in patients with various cardiovascular disorders, suggest that ROCKi might in future broaden the spectrum of treatments available for patients with diabetic nephropathy.
authors.affiliation: Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, Oregon 97239-2940, USA. komersr@ohsu.edu
authors.forename: Radko
authors.initials: R
authors.lastname: Komers
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007668:Kidney / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil