Rho/Rho kinase as a potential target for the treatment of renal disease.
The small G-protein Rho and its downstream effector Rho kinase constitute important mediators not only of vascular contraction but also of actin cytoskeleton reorganization, cellular morphology, motility, adhesion and proliferation. The Rho/Rho kinase pathway plays an important role in the structure and function of various kidney cells including tubular epithelial cells, mesangial cells and podocytes. The Rho/Rho kinase pathway also regulates glomerular blood flow and glomerular filtration rate by modulating renal arteriolar contractility. Potent and specific inhibitors of Rho kinase have recently been developed and their therapeutic effects on a variety of renal injury models have been examined. In the rat models of hypertensive glomerulosclerosis, unilateral ureteral obstruction (for interstitial renal fibrosis) and ischemia/reperfusion acute renal failure, treatment with novel Rho kinase inhibitors attenuates the development of renal damage. Although human data connecting the activation of Rho/Rho kinase pathway and kidney disease are still lacking, these studies have provided compelling evidence for the renoprotective effects of Rho kinase inhibitors.
Wakino
Shu
S
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan. swakino@sc.itc.keio.ac.jp
Kanda
Takeshi
T
Hayashi
Koichi
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; C049347:fasudil