title: Role of TNF-associated cytokines in renal tubular cell apoptosis induced by hyperoxaluria.
abstract: Crystal-cell interaction has been reported as one of the most crucial steps in urinary stone formation. Hyperoxaluria-induced apoptotic changes in renal tubular epithelial cells is the end-stage of this interaction. We aimed to evaluate the possible pathways responsible in the induction of apoptosis within the involved cells by assessing the receptoral expression of three different pathways. 16 male Spraque-Dowley rats were divided into two groups: Group 1 (n:8) received only distilled water; Group 2 (n:8) received 0.75 % ethylene glycol (EG) in their daily water to induce hyperoxaluria for 2 weeks. After 24 h urine collection, all animals were euthenized and right kidneys were removed and fixed for immunohistochemical evaluation. Oxalate and creatinine levels (in 24 h-urine) and FAS, tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor-2 expressions (in tissue) have been assessed. In addition to TNF (p = 0.0007) expression; both FAS (p = 0.0129 ) and FASL (p = 0.032) expressions significantly increased in animals treated with EG. The expressions of TRAIL (p = 0.49) and TRAIL-R2 (p = 0.34) receptors did not change statistically after hyperoxaluria induction. Although a positive correlation with cytokine expression density and 24 h-urinary oxalate expression (mg oxalate/mg creatinine) has been assessed with TNF (p = 0.04, r = 0.82), FAS (p = 0.05, r = 0.80), FAS-L (p = 0.04, r = 0.82); no correlation could be demonstrated between TRAIL and TRAIL R2 expressions. Our results indicate that apoptosis induced by oxalate is possibly mediated via TNF and FAS pathways. However, TRAIL and TRAIL-R2 seemed to have no function in the cascade. Correlation with urinary oxalate levels did further strengthen the findings.
authors.affiliation: Urology Clinic, Kartal Training Hospital, Istanbul, Turkey. rahimhoruz@gmail.com
authors.forename: Rahim
authors.initials: R
authors.lastname: Horuz
authors.forename: Cemal
authors.initials: C
authors.lastname: Göktaş
authors.forename: Cihangir A
authors.initials: CA
authors.lastname: Çetinel
authors.forename: Oktay
authors.initials: O
authors.lastname: Akça
authors.forename: Hasan
authors.initials: H
authors.lastname: Aydın
authors.forename: Işın D
authors.initials: ID
authors.lastname: Ekici
authors.forename: Selami
authors.initials: S
authors.lastname: Albayrak
authors.forename: Kemal
authors.initials: K
authors.lastname: Sarıca
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D053222:Fas Ligand Protein / Q000502:physiology; D006959:Hyperoxaluria / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D007684:Kidney Tubules / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D053040:Nephrolithiasis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000502:physiology*
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505644:Tnfrsf10b protein, rat; C505655:Tnfsf10 protein, rat; D048069:Tumor Necrosis Factors