|Author||Ishizaka, Masanori ♦ Gohda, Tomohito ♦ Takagi, Miyuki ♦ Omote, Keisuke ♦ Sonoda, Yuji ♦ Oliva Trejo, Juan Alejandro ♦ Asao, Rin ♦ Hidaka, Teruo ♦ Asanuma, Katsuhiko ♦ Horikoshi, Satoshi ♦ Tomino, Yasuhiko|
|Source||United States Department of Energy Office of Scientific and Technical Information|
|Subject Keyword||APPLIED LIFE SCIENCES ♦ ALBUMINS ♦ APOPTOSIS ♦ CREATININE ♦ DIAPHRAGM ♦ ELECTRON MICROSCOPY ♦ GLOMERULI ♦ GUANOSINE ♦ HYPERTROPHY ♦ INJURIES ♦ KNOCK-OUT REACTIONS ♦ LABELLING ♦ MICE ♦ STREPTOZOCIN ♦ TOXINS|
|Abstract||Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age. A more marked ACR increase was observed in STZ/KO group than STZ/WT group, although ACR did increase with weeks of age in both diabetic groups. The kidney sections from diabetic mice revealed a glomerular hypertrophy with mesangial expansion, but there was no appreciable difference in glomerular findings under a light microscope between STZ/WT and STZ/KO mice. However, an electron microscopy analysis revealed that regardless of the presence or absence of diabetes, both KO (KO and STZ/KO) groups had a higher rate of foot process effacement compared with both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm protein, podocin, was reduced with the induction of diabetes, and the levels in the STZ/KO group experienced a further reduction compared with the STZ/WT group. The number of WT1-positive cells in the STZ/KO group was more significantly decreased than that in the other three groups. In contrast, the numbers of cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group were more increased than those in the STZ/WT group. Thus, this study provides evidence that podocyte-specific deletion of Rac1 results in morphological alteration in podocytes, and that the induction of apoptosis or decreased expression of the slit diaphragm proteins by hyperglycemic stimuli are associated with the progression of diabetic nephropathy.|
|Learning Resource Type||Article|
|Publisher Place||United States|
|Journal||Biochemical and Biophysical Research Communications|
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