Carbamylated proteins activate glomerular mesangial cells and stimulate collagen deposition
| Autor: | Ashok K. Singh, Alfredo A. Pegoraro, Wa Mo, George Dunea, Mashouf Shaykh, Jose A.L. Arruda |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Glomerular Mesangial Cell Pathology and Forensic Medicine Immunoenzyme Techniques Fibrosis Internal medicine medicine Animals Urea Gelatinase Renal Insufficiency Cells Cultured Cyanates Kidney Mesangial cell Chemistry Glomerulosclerosis General Medicine Fetal Blood medicine.disease Uremia Glomerular Mesangium Endocrinology medicine.anatomical_structure Gelatinases Protein Biosynthesis Cattle Collagen Cell Division Fetal bovine serum |
| Zdroj: | Journal of Laboratory and Clinical Medicine. 133:302-308 |
| ISSN: | 0022-2143 |
| Popis: | Carbamylated proteins formed in renal insufficiency from the spontaneous decomposition of urea exert a variety of metabolic effects. Here we examined the effects of carbamylated proteins on glomerular mesangial cells to determine whether urea retention in early renal insufficiency may itself promote glomerular sclerosis and hasten the progression to kidney failure. To this effect we carbamylated fetal bovine serum proteins in vitro and tested their effect on mesangial cell proliferation (by tritiated thymidine uptake), de novo protein synthesis (by tritiated leucine uptake), collagen I and collagen IV accumulation (by avidin-biotin enzyme immunoassay), and gelatinase levels in the medium (by zymography and quantitative fluorescence assay). Carbamylated fetal bovine serum at concentrations present in uremia increased tritiated thymidine incorporation by 50% without altering tritiated leucine incorporation, and it increased collagens I and IV in the monolayer by 150% to 300%. Gelatinase activity was unchanged. We conclude that carbamylated proteins can activate mesangial cells to a profibrogenic phenotype. From a clinical perspective, the carbamylation of proteins by elevated urea levels may accelerate the progression to kidney failure and thus set up a vicious cycle in which the nitrogen retention itself would cause further progression of fibrosis and deterioration of kidney function. |
| Databáze: | OpenAIRE |
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