Angiotensin-converting enzyme inhibition modulates high-glucose-induced extracellular matrix changes in mouse glomerular epithelial cells
| Autor: | M. Sensi, F. Vasaturo, U. Di Mario, Susanna Morano, Rosalba Cipriani, Carmela Santangelo, S. Scarpa, Leo Guidobaldi, Pantellini F, M. G. Cerrito |
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| Předmět: |
Physiology
Kidney Glomerulus Angiotensin-Converting Enzyme Inhibitors Peptidyl-Dipeptidase A Biology Pathogenesis Diabetic nephropathy Extracellular matrix Mice Genetics medicine Animals RNA Messenger Cells Cultured Extracellular Matrix Alterations Epithelial Cells Angiotensin-converting enzyme General Medicine medicine.disease Extracellular Matrix Fibronectins Glucose Biochemistry Nephrology Enalaprilat High glucose biology.protein Laminin |
| Zdroj: | Scopus-Elsevier |
| Popis: | Background/Aim: Extracellular matrix alterations are involved in the pathogenesis of diabetic nephropathy. We evaluated the effects of high glucose concentrations and inhibition of angiotensin-converting enzyme on the laminin and fibronectin production by glomerular epithelial cells. Methods: Glomerular epithelial cells were cultured in 5 and 30 mmol/l glucose, with and without enalaprilat (0.3 mmol/l). Laminin and fibronectin were measured (35S-methionine, immunoprecipitation), and their mRNA expression was evaluated (RT-PCR). Results: The laminin concentration was higher in the cells than in the medium, where an increase of its content was observed under high-glucose conditions (p < 0.01). Fibronectin, found only in the medium, was not modified by the high glucose concentration. Following enalaprilat administration, the laminin concentration was decreased under high-glucose conditions, both in the cell and in the medium (p < 0.001), whereas the fibronectin concentration was increased under high-glucose conditions (p < 0.001). The mRNA expression of laminin and fibronectin under high-glucose conditions only slightly increased. Enalaprilat decreased the fibronectin mRNA synthesis dramatically (>50%, p < 0.0001) under high-glucose conditions. Conclusions: Enalaprilat normalizes the abnormal, high-glucose-induced concentration of laminin, while it decreases the fibronectin synthesis. The improvement of the renal function in diabetic patients treated with angiotensin-converting enzyme inhibitors may, in part, be due to a modulator effect on extracellular matrix content and composition. |
| Databáze: | OpenAIRE |
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