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
načítá se...