Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy
| Autor: | Hitoshi Sugiyama, Hiroyuki Kitayama, Yohei Maeshima, Hirofumi Makino, Yasushi Yamasaki, Yoshihiko Yamamoto, Shinji Kitamura, Yuki Takazawa |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Blood Glucose
Collagen Type IV medicine.medical_specialty Tumstatin Angiogenesis Endocrinology Diabetes and Metabolism Kidney Glomerulus Angiogenesis Inhibitors urologic and male genital diseases Autoantigens Monocytes Podocyte Diabetes Mellitus Experimental Diabetic nephropathy Nephrin Mice Diabetic Neuropathies Internal medicine Internal Medicine medicine Albuminuria Animals RNA Messenger biology Neovascularization Pathologic business.industry urogenital system Macrophages Membrane Proteins Proteins Hypertrophy Glomerular Hypertrophy medicine.disease female genital diseases and pregnancy complications Mice Inbred C57BL Platelet Endothelial Cell Adhesion Molecule-1 medicine.anatomical_structure Endocrinology Creatinine Glomerular Filtration Barrier biology.protein Female business Glomerular hyperfiltration |
| Zdroj: | Diabetes. 53(7) |
| ISSN: | 0012-1797 |
| Popis: | In the early stage of diabetic nephropathy (one of the major microvascular complications of diabetes) glomerular hyperfiltration and hypertrophy are observed. It is clinically important to regulate glomerular hypertrophy for preventing glomerulosclerosis. The number of glomerular endothelial cells is known to be increased in diabetic nephropathy associated with enlarged glomerular tufts, suggesting that the mechanism is similar to that of angiogenesis. Tumstatin peptide is an angiogenesis inhibitor derived from type IV collagen and inhibits in vivo neovascularization induced by vascular endothelial growth factor (VEGF), one of the mediators of glomerular hypertrophy in diabetic nephropathy. Here, we show the effect of tumstatin peptide in inhibiting alterations in early diabetic nephropathy. Glomerular hypertrophy, hyperfiltration, and albuminuria were suppressed by tumstatin peptide (1 mg/kg) in streptozotocin-induced diabetic mice. Glomerular matrix expansion, the increase of total glomerular cell number and glomerular endothelial cells (CD31 positive), and monocyte/macrophage accumulation was inhibited by tumstatin peptide. Increase in renal expression of VEGF, flk-1, and angiopoietin-2, an antagonist of angiopoietin-1, was inhibited by tumstatin treatment in diabetic mice. Alteration of glomerular nephrin expression, a podocyte protein crucial for maintaining glomerular filtration barrier, was recovered by tumstatin in diabetic mice. Taken together, these results demonstrate the potential use of antiangiogenic tumstatin peptide as a novel therapeutic agent in early diabetic nephropathy. |
| Databáze: | OpenAIRE |
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