Abstract
The small GTPase Rho and its effector Rho-kinase (ROCK) are implicated in the pathogenesis of diabetic kidney disease. In chronic kidney diseases including diabetic nephropathy, progressive tubulointerstitial fibrosis is the final common pathway to end-stage renal disease and deeply related to renal prognosis. We have previously reported that a chemical ROCK inhibitor suppressed the progression of diabetic nephropathy. 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 ROCK2 remains unclear. In the present study, we investigated the role of renal tubular ROCK2 in the pathogenesis of chronic kidney disease using an established model to cause renal fibrosis, unilateral ureteral obstruction (UUO). Masson’s trichrome staining revealed that the collagen deposition was significantly increased in the kidneys of UUO group compared with Sham-operated group. We detected upregulation of ROCK2 at both mRNA and protein levels in UUO group, relative to sham operated group. The kinase activity of ROCK2 was also elevated in UUO group. Based on our research, we suggest that ROCK2 may have an important role in tubulointerstitial fibrosis. ROCK2 may be a potential therapeutic target for the treatment of diabetic nephropathy. Disclosure K. Sekiguchi: None. K. Matoba: Research Support; Self; Eli Lilly Japan K. K. R. Ukichi: None. Y. Nagai: None. Y. Takeda: None. T. Akamine: None. Y. Kanazawa: None. K. Utsunomiya: None. R. Nishimura: Speaker’s Bureau; Self; Abbott Japan Co., Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K. K., Kissei Pharmaceutical Co., Ltd., Medtronic, MSD Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.
Published Version
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