NF- B activation and overexpression of regulated genes in human diabetic nephropathy
| Autor: | Leopoldo Ardiles, M. Eugenia Burgos, Herman Schneider, Sergio Mezzano, Claudio Aros, Claudio Flores, Alejandra Droguett, Marta Ruiz-Ortega, Jesús Egido |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male medicine.medical_specialty Chemokine Gene Expression In situ hybridization Kidney Interstitial cell Nephropathy Diabetic nephropathy Internal medicine medicine Humans Diabetic Nephropathies RNA Messenger Chemokine CCL5 Chemokine CCL2 In Situ Hybridization Inflammation Transplantation biology business.industry Monocyte NF-kappa B Transcription Factor RelA NF-kappa B p50 Subunit Middle Aged medicine.disease Immunohistochemistry Angiotensin II Up-Regulation medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 2 Gene Expression Regulation Nephrology Disease Progression biology.protein Cancer research Female business Biomarkers |
| Zdroj: | NEPHROLOGY DIALYSIS TRANSPLANTATION Artículos CONICYT CONICYT Chile instacron:CONICYT |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfh207 |
| Popis: | Background. Nuclear factor-kB (NF-kB) regulates genes involved in renal disease progression, such as the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES. NF-kB is activated in experimental models of renal injury, and in vitro studies also suggest that proteinuria and angiotensin II could be important NF-kB activators. It has been proposed that locally produced MCP-1 may be involved in the development of diabetic nephropathy (DN). We examined the hypothesis that NF-kB could be an indicator of renal damage progression in DN. Methods. Biopsy specimens from 11 patients with type 2 diabeties and overt nephropathy were studied by southwestern histochemistry for the in situ detection of activated NF-kB. In addition, by immunohistochemistry and/or in situ hybridization, we studied the expression of MCP-1 and RANTES, whose genes are regulated by NF-kB. Results. NF-kB was detected mainly in cortical tubular epithelial cells and, to a lesser extent, in some glomerular and interstitial cells. A strong upregulation of MCP-1 and RANTES was observed in all the cases, mainly in tubular cells, and there was a strong correlation between the expression of these chemokines and NF-kB activation in the same cells, as observed in serial sections (r ¼ 0.7; P ¼ 0.01). In addition, the tubular expression of these chemokines was correlated mainly with the magnitude of the proteinuria (P ¼ 0.002) and with interstitial cell infiltration (P |
| Databáze: | OpenAIRE |
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