Journal of the American Society of Nephrology, 2008-05, Vol.19 (5), p.904-914
2008
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Details
- Autor(en) / Beteiligte
- Titel
- The Death Ligand TRAIL in Diabetic Nephropathy
- Ist Teil von
- Journal of the American Society of Nephrology, 2008-05, Vol.19 (5), p.904-914
- Ort / Verlag
- Hagerstown, MD: Lippincott Williams & Wilkins
- Erscheinungsjahr
- 2008
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Apoptotic cell death contributes to diabetic nephropathy (DN), but its role is not well understood. The tubulointerstitium from DN biopsy specimens was microdissected, and expression profiles of genes related to apoptosis were analyzed. A total of 112 (25%) of 455 cell death-related genes were found to be significantly differentially regulated. Among those that showed the greatest changes in regulation were two death receptors, OPG (the gene encoding osteoprotegerin) and Fas, and the death ligand TRAIL. Glomerular and proximal tubular TRAIL expression, assessed by immunohistochemistry, was higher in DN kidneys than controls and was associated with clinical and histologic severity of disease. In vitro, proinflammatory cytokines but not glucose alone regulated TRAIL expression in the human proximal tubular cell line HK-2. TRAIL induced tubular cell apoptosis in a dosage-dependant manner, an effect that was more marked in the presence of high levels of glucose and proinflammatory cytokines. TRAIL also activated NF-kappaB, and inhibition of NF-kappaB sensitized cells to TRAIL-induced apoptosis. It is proposed that TRAIL-induced cell death could play an important role in the progression of human DN.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1046-6673eISSN: 1533-3450DOI: 10.1681/ASN.2007050581Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2386716
- Format
- –
- Schlagworte
- Apoptosis - drug effects, Apoptosis - physiology, Associated diseases and complications, Basic Research, Biological and medical sciences, Biopsy, Cell Line, Cell Survival - physiology, Diabetes. Impaired glucose tolerance, Diabetic Nephropathies - metabolism, Diabetic Nephropathies - pathology, Diabetic Nephropathies - physiopathology, Endocrine pancreas. Apud cells (diseases), Endocrinopathies, Epithelial Cells - cytology, Epithelial Cells - drug effects, Epithelial Cells - physiology, Female, Gene Expression Regulation, Glucose - pharmacology, Humans, Immunohistochemistry, Kidney Tubules, Proximal - cytology, Kidney Tubules, Proximal - physiology, Kidneys, Ligands, Male, Medical sciences, Middle Aged, Nephrology. Urinary tract diseases, NF-kappa B - metabolism, Osteoprotegerin - genetics, Osteoprotegerin - metabolism, Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics, Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism, RNA, Messenger - metabolism, TNF-Related Apoptosis-Inducing Ligand - genetics, TNF-Related Apoptosis-Inducing Ligand - metabolism, Urinary system involvement in other diseases. Miscellaneous