Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence indicates that the renin-angiotensin system (RAS) seems to play a considerable role in the development of tubulointerstitial (TI) lesions caused by hyperoxaluria (Hox). The purpose of the present study was to evaluate the specific mechanism by which Hox involving RAS induces chemokine and cytokine expression and, therefore, renal TI damage in the ethylene-glycol (ETG) induced hyperoxaluric rat model. Sprague-Dawley rats, separated into five groups, received: G1 regular water, and G2, G3, G4 and G5 1% ETG (a precursor for oxalates) in their drinking water for 4 weeks. An angiotensin converting enzyme inhibitor, benazepril (BZ) 10 mg/kg/day, angiotensin II receptor antagonists, subtype 1 (AT1) losartan (LOS) 40 mg/kg/day and subtype 2 (AT2) PD 123,319 (PD) 10 mg/kg/day, were administered daily to G3, G4 and G5, respectively. At the end of the study, the inflammatory response to Hox was evaluated using anti-NF-kappaB (p50), anti-IL-6, anti-MCP-1; anti-RANTES and anti-ED1 (monocytes/macrophages) in each group. In spite of the same urine oxalate levels, rats belonging to the hyperoxaluric groups treated with either BZ or LOS showed significantly (P<0.01) less TI lesions together with a lower immunoexpression of inflammatory mediators when compared with untreated hyperoxaluric animals. NF-kappaB (p50) was increased in tubular cells in the ETG group (43.6+/-8.7 positive cells/mm(2)) and was significantly (P<0.01) reduced by LOS (11.2+/-4 positive cells/mm(2)) and even more by BZ (6.1+/-2.4 positive cells/mm(2)). There was a significant (P<0.01) correlation between NF-kappaB (p50) positive cells and ED1 cells in the ETG group (r=0.88) and in the ETG+LOS group (r=0.92). LOS showed better control on IL-6 and MCP-1 with respect to untreated rats, while BZ showed the best control on RANTES and ED1 cells in comparison with untreated animals. Renal function was significantly (P<0.01) better preserved in BZ and LOS treated groups compared to both untreated animals and rats with PD, as indicated by creatinine clearance values. These results suggest that Hox stimulates the NF-kappaB cascade and, therefore, induces the overexpression of inflammatory mediators like IL-6, MCP-1, and RANTES. This pathway seems to be mediated not only by AT1 but also by AT2 receptors of angiotensin II.
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PMID:NF-kappaB and chemokine-cytokine expression in renal tubulointerstitium in experimental hyperoxaluria. Role of the renin-angiotensin system. 1628 84

Osteopontin (OPN) is the major constituent of calcium-containing urinary stones and is involved in the inhibition of nucleation and aggregation of calcium oxalate (CaOx) crystals, promotion of the adherence of CaOx crystals to cultured renal epithelial cells, and regulation of inflammatory cells as chemokine. OPN has different effects (inhibitor and promoter) at each stage of stone formation in vitro and these multifunctional actions of OPN have not been fully elucidated. We developed a modified crystal method using collagen granules (CG) and immobilized OPN. OPN had strong inhibitory activity on the aggregation/growth of CaOx crystals, but the inhibitory activity decreased by use of OPN-immobilized CG. OPN is also a critical promoter of adherence for CaOx crystals to cultured renal epithelial cells in an in vitro experimental system. We examined the effect of OPN in vivo, by OPN siRNA transfection in rats. Hydrodynamic intravenous and renal subcapsular injections with lipofection were performed on days 1 and 8. The calcium concentration in the kidney was significantly lower and the frequency of CaOx crystal deposits in the tubules was lower in the OPN siRNA transfection group (drinking 1.5% ethylene glycol (EG)), than in the EG drinking group (sham operation) at day 15. We examined the effect of candesartan, an angiotensin II (Ang II) type 1 receptor blockers (ARB) in hyperoxaluric rats. ARB reduced crystal formation and calcium concentrations in the whole kidney. Hyperoxaluria leads to CaOx crystallization and the development of tubulointerstitial lesions in the kidney. AngII mediates OPN synthesis, which is involved in both macrophage recruitment and CaOx crystallization. OPN synthesis and production increased with hyperoxaluria but to a lesser extent in ARB-treated hyperoxaluric rats. These results show that oxalate can activate the renal renin-angiotensin system and that oxalate-induced upregulation of OPN is in part mediated via the renal renin-angiotensin system.
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PMID:[Multifunctional character of osteopontin and strategy for clinical applications]. 2130 62