title: Phenotypic characterization of a novel HO-1 depletion model in the rat.
abstract: Although the protective role of HO-1 induction in various forms of kidney disease is well established, mechanisms other than heme catabolism to biliverdin, bilirubin and carbon monoxide have recently been identified. Unraveling these mechanisms requires the generation of appropriate animal models. The present study describes the generation of a HO-1 deficient Hmox1-/-rat model and characterizes its renal and extrarenal phenotype. Hmox1-/-rats had growth retardation and splenomegaly compared to their Hmox1+/+littermates. Focal segmental glomerulosclerosis-type lesions and interstitial inflammatory infiltrates were prominent morphologic findings and were associated with increased blood urea nitrogen, serum creatinine and albuminuria. There was no increase in iron deposition in glomeruli, tubules or interstitium. Iron deposition in spleen and liver was reduced. Electron microscopic examination of glomeruli revealed edematous podocytes with scant areas of foot process effacement but otherwise well preserved processes and slit-diaphragms. Of the filtration barrier proteins examined, β-catenin expression was markedly reduced both in glomeruli and extrarenal tissues. Since the rat is the preferred laboratory animal in experimental physiology and pathophysiology, the rat model of HO-1 deficiency may provide a novel tool for investigation of the role of this enzyme in renal function and disease.
authors: 1st Division of Critical Care Medicine and Pulmonary Services, 'Evangelismos' Hospital, Department of Medicine, National and Kapodistrian University of Athens, School of Health Sciences, Athens, Greece.
authors: Vassilios
authors: V
authors: Atsaves
authors: 1st Division of Critical Care Medicine and Pulmonary Services, 'Evangelismos' Hospital, Department of Medicine, National and Kapodistrian University of Athens, School of Health Sciences, Athens, Greece.
authors: Maria G
authors: MG
authors: Detsika
authors: Department of Pathology, National and Kapodistian University of Athens, School of Health Sciences, Athens, Greece.
authors: Elpida
authors: E
authors: Poulaki
authors: Department of Pathology, National and Kapodistian University of Athens, School of Health Sciences, Athens, Greece.
authors: Hara
authors: H
authors: Gakiopoulou
authors: 1st Division of Critical Care Medicine and Pulmonary Services, 'Evangelismos' Hospital, Department of Medicine, National and Kapodistrian University of Athens, School of Health Sciences, Athens, Greece. ealianos2@gmail.com.|Division of Nephrology, Department of Medicine, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA. ealianos2@gmail.com.|Thorax Foundation, Ploutarchou 3, 10675, Athens, Greece. ealianos2@gmail.com.
authors: Elias A
authors: EA
authors: Lianos
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood; D055786:Gene Knockout Techniques; D051547:Heme Oxygenase-1 / Q000235:genetics*; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D050199:Podocytes / Q000378:metabolism; D051381:Rats; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin; D003404:Creatinine; D007501:Iron; D051547:Heme Oxygenase-1
keywords: Heme oxygenase-1 (HO-1); Kidney; Rat model