Endothelial cell-selective adhesion molecule regulates albuminuria in diabetic nephropathy
| Autor: | Tatsuro Ishida, Tetsuya Hara, Husni M. Cangara, Ken-ichi Hirata |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Endothelium Kidney Glomerulus Down-Regulation Vascular permeability Kidney Biochemistry Cell Line Diabetes Mellitus Experimental Tight Junctions Capillary Permeability Diabetic nephropathy Mice Internal medicine medicine Albuminuria Animals Humans RNA Small Interfering Serum Albumin Mice Knockout Dose-Response Relationship Drug Chemistry Kidney metabolism Cell Biology medicine.disease Extravasation Glucose medicine.anatomical_structure Endocrinology Microalbuminuria Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine Cell Adhesion Molecules |
| Zdroj: | Microvascular Research. 77:348-355 |
| ISSN: | 0026-2862 |
| DOI: | 10.1016/j.mvr.2009.01.002 |
| Popis: | Microalbuminuria is a primary manifestation of diabetic nephropathy. Endothelial cell-selective adhesion molecule (ESAM) is a new member of the immunoglobulin superfamily which is selectively expressed by vascular endothelial cells. Although ESAM mediates homophilic interaction between endothelial cells, the role of ESAM in glomerular permeability remains unknown. We examined the expression and function of ESAM in the high glucose-induced microangiopathy in the kidney. ESAM was highly expressed in the glomerular endothelial cells, and the level was significantly reduced in the streptozotocin-induced diabetic mice. Stimulation of cultured endothelial cells with high glucose (35 mmol/l) resulted in a significant decrease in the ESAM expression compared to normal glucose (5.5 mmol/l). In vitro permeability assays revealed that albumin diffusion across endothelial monolayers was significantly increased when ESAM was knocked down by siRNA, suggesting that ESAM regulates vascular permeability of the glomeruli. To confirm these results in vivo, albuminuria was assessed using ESAM-/- mice. Urinary albumin to creatinine ratio in ESAM-/- mice was significantly higher than in ESAM+/+ mice. Transmission electron microscopy revealed that glomerular endothelial fenestration was decreased and endothelial tight junction was irregular and relatively wider in ESAM-/- mice than in ESAM+/+ mice. In conclusion, hyperglycemia downregulates ESAM and increases glomerular endothelial permeability. Thus, ESAM may regulate albumin extravasation at the glomeruli and play a role in the initiation of diabetic nephropathy. |
| Databáze: | OpenAIRE |
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