Abstract
The small GTPase Rho and its effector Rho-kinase (ROCK) are involved in the pathogenesis of diabetic nephropathy. In chronic kidney diseases including diabetic nephropathy, tubulointerstitial fibrosis is closely related to renal outcome. We have previously reported that ROCK inhibition suppressed the progression of diabetic nephropathy in murine models. ROCK has two isoforms, ROCK1 and ROCK2. ROCK1 is known to be involved in the endocytosis of albumin in tubular epithelial cells via megalin/cubilin-dependent mechanism. On the other hand, the role of renal tubular ROCK2 has not been elucidated.In the present study, we aimed to establish the role of renal tubular ROCK2 in the pathogenesis of chronic kidney disease using a tubulointerstitial injury model known as folic acid-induced nephropathy (FAN) . Masson’s trichrome staining showed an elevated collagen deposition in the kidneys of FAN group compared with vehicle-treated group. We detected a relative upregulation of ROCK2 at protein levels in FAN group, compared with vehicle-treated group. Immunoprecipitation assay demonstrated that the kinase activity of ROCK2 relatively increased in FAN group. Based on these findings, we conclude that ROCK2 has an important contribution to tubulointerstitial fibrosis. ROCK2 may become a therapeutic target for the treatment of chronic kidney disease. Disclosure K.Sekiguchi: None. K.Matoba: None. R.Ukichi: None. Y.Nagai: None. Y.Takeda: None. Y.Kanazawa: None. K.Utsunomiya: None. R.Nishimura: Speaker's Bureau; Abbott Diabetes, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck & Co., Inc., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Terumo Corporation.
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