title: Osteopontin deficiency reduces kidney damage from hypercholesterolemia in Apolipoprotein E-deficient mice.
abstract: Hypercholesterolemia is a well-established risk factor for kidney injury, which can lead to chronic kidney disease (CKD). Osteopontin (OPN) has been implicated in the pathology of several renal conditions. This study was to evaluate the effects of OPN on hypercholesterolemia induced renal dysfunction. Eight-week-old male mice were divided into 4 groups: apolipoprotein E knockout (ApoE(-/-)) and ApoE/OPN knockout (ApoE(-/-)/OPN(-/-)) mice fed a normal diet (ND) or high cholesterol diet (HD). After 4 weeks, Periodic acid-Schiff (PAS) and oil red O staining revealed excessive lipid deposition in the glomeruli of ApoE(-/-)HD mice, however, significantly suppressed in ApoE(-/-)/OPN(-/-)HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression was lower in the glomeruli of ApoE(-/-)/OPN(-/-)HD mice than ApoE(-/-)HD mice. In vitro study, primary mesangial cells were incubated with recombinant mouse OPN (rmOPN). RmOPN induced LOX-1 mRNA and protein expression in primary mesangial cells. Pre-treatment with an ERK inhibitor suppressed the LOX-1 gene expression induced by rmOPN. These results indicate that OPN contributes to kidney damage in hypercholesterolemia and suggest that inhibition of OPN may provide a potential therapeutic target for the prevention of hypercholesterolemia.
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Zouwei
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Okura
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nagao
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Enomoto
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kukida
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanino
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine, Ehime, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kurata
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Higaki
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D018345:Mice, Knockout; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D065840:Protective Factors; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; C506896:Spp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D053495:Osteopontin