title: Renoprotective effects of paricalcitol on gentamicin-induced kidney injury in rats.
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.
authors: Department of Internal Medicine, Chonnam National Univ. Medical School, Gwangju, Korea.
authors: Jeong Woo
authors: JW
authors: Park
authors: Eun Hui
authors: EH
authors: Bae
authors: In Jin
authors: IJ
authors: Kim
authors: Seong Kwon
authors: SK
authors: Ma
authors: Chan
authors: C
authors: Choi
authors: JongUn
authors: J
authors: Lee
authors: Soo Wan
authors: SW
authors: Kim
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004872:Ergocalciferols / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control; D005839:Gentamicins / Q000493:pharmacokinetics; D018836:Inflammation Mediators / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009393:Nephritis / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C496022:Aqp1 protein, rat; D050071:Bone Density Conservation Agents; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004872:Ergocalciferols; D005839:Gentamicins; D018836:Inflammation Mediators; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D051398:Aquaporin 1; C084656:paricalcitol; D012964:Sodium; D048049:Extracellular Signal-Regulated MAP Kinases