1. Renoprotective effects of paricalcitol on gentamicin-induced kidney injury in rats.
- Author
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Park JW, Bae EH, Kim IJ, Ma SK, Choi C, Lee J, and Kim SW
- Subjects
- Animals, Aquaporin 1 metabolism, Carrier Proteins metabolism, Cell Adhesion Molecules metabolism, Cell Line, Cytokines metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Fibrosis prevention & control, Inflammation Mediators metabolism, Kidney Tubules cytology, Kidney Tubules drug effects, Kidney Tubules metabolism, Kidney Tubules, Proximal drug effects, Kidney Tubules, Proximal pathology, Male, NF-kappa B metabolism, Nephritis chemically induced, Nephritis prevention & control, Rats, Rats, Sprague-Dawley, Sodium metabolism, Transforming Growth Factor beta1 metabolism, Bone Density Conservation Agents pharmacology, Ergocalciferols pharmacology, Gentamicins pharmacokinetics, Kidney Diseases chemically induced, Kidney Diseases prevention & control
- Abstract
Vitamin D is thought to exert a protective effect on renal disease progression, but the underlying molecular mechanism remains unclear. We investigated whether paricalcitol ameliorates tubular dysfunction and fibrosis in gentamicin (GM)-induced renal injury. Two groups of rats were treated with GM (100 mg x kg(-1) x day(-1)), one of which was cotreated with paricalcitol (0.3 microg x kg(-1) x day(-1)) for 14 days and the other was not. The control group was treated with vehicle only. HK-2 cells were cultured with GM in the absence or presence of paricalcitol. Paricalcitol restored impaired renal function and the downregulated renal sodium transporters and aquaporin-1 expression caused by GM. ED-1-expressing monocyte/macrophage accumulation induced by GM was attenuated by paricalcitol treatment. Paricalcitol prevented upregulated inflammatory cytokines (TNF-alpha, IL-1beta, INF-gamma) and adhesion molecules (monocyte chemoattractant protein-1, ICAM-1, VCAM-1) induced by GM. In addition, paricalcitol effectively reversed TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) process and extracellular matrix accumulation in GM-induced nephropathy. Increased collagen deposition and fibrosis in GM-treated kidney were ameliorated by paricalcitol. Paricalcitol also attenuated the upregulated NF-kappaB and phosphorylated ERK1/2 expression in HK-2 cells cultured with GM. In conclusion, paricalcitol prevents GM-induced renal injury by inhibiting renal inflammation and fibrosis, the mechanism of which is the interruption of NF-kappaB/ERK signaling pathway and preservation of tubular epithelial integrity via inhibiting EMT process.
- Published
- 2010
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