The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats
| Autor: | Hyun Jung Kim, Patrick TaeJoon Hwang, Gi Yeon Han, Sang Hoon Kim, Chan Wha Kim, Young Woo Jang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
rac1 GTP-Binding Protein
medicine.medical_specialty Clinical Biochemistry urologic and male genital diseases Kidney Biochemistry Podocyte Desmin Diabetes Mellitus Experimental Diabetic nephropathy Nephrin Wortmannin chemistry.chemical_compound Internal medicine Albumins medicine Animals Humans Diabetic Nephropathies cdc42 GTP-Binding Protein Molecular Biology Phosphoinositide-3 Kinase Inhibitors biology urogenital system Podocytes Intracellular Signaling Peptides and Proteins Membrane Proteins Rats Inbred Strains medicine.disease Actin cytoskeleton Rats Androstadienes Disease Models Animal medicine.anatomical_structure Endocrinology Cdc42 GTP-Binding Protein chemistry Creatinine Podocin biology.protein Molecular Medicine SprD Original Article |
| Popis: | Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to kidney glomeruli. Podocytes are glomerular epithelial cells and play critical roles in the glomerular filtration barrier. Recent studies have shown the importance of regulating the podocyte actin cytoskeleton in early DN. The phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, simultaneously regulates Rac1 and Cdc42, which destabilize the podocyte actin cytoskeleton during early DN. In this study, in order to evaluate the reno-protective effects of wortmannin in early DN by regulating Rac1 and Cdc42, streptozotocin (STZ)-induced proteinuric renal disease (SPRD) rats were treated with wortmannin. The albuminuria value of the SPRD group was 3.55 ± 0.56 mg/day, whereas wortmannin group was 1.77 ± 0.48 mg/day. Also, the albumin to creatinine ratio (ACR) value of the SPRD group was 53.08 ± 10.82 mg/g, whereas wortmannin group was 20.27 ± 6.41 mg/g. Changes in the expression level of nephrin, podocin and Rac1/Cdc42, which is related to actin cytoskeleton in podocytes, by wortmannin administration were confirmed by Western blotting. The expression levels of nephrin (79.66 ± 0.02), podocin (87.81 ± 0.03) and Rac1/Cdc42 (86.12 ± 0.02) in the wortmannin group were higher than the expression levels of nephrin (55.32 ± 0.03), podocin (53.40 ± 0.06) and Rac1/Cdc42 (54.05 ± 0.04) in the SPRD group. In addition, expression and localization of nephrin, podocin and desmin were confirmed by immunofluorescence. In summary, we found for the first time that wortmannin has a reno-protective effect on SPRD rats during the early DN. The beneficial effects of wortmannin in SPRD rats indicate that this compound could be used to delay the progression of the disease during the early DN stage. |
| Databáze: | OpenAIRE |
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