title: Atherogenic scavenger receptor modulation in the tubulointerstitium in response to chronic renal injury.
abstract: Oxidized low-density lipoproteins (oxLDL) and their scavenger receptor (SR) binding partners play a central role in atherosclerosis and by analogy may play a role in chronic kidney disease pathogenesis. The present study was designed to investigate in C57BL/6 mice the effects of hypercholesterolemia on renal injury severity and oxLDL generation after unilateral ureteral obstruction (UUO). The expression profiles of CD36, SR class AI/II (SR-A), lectin-like receptor for oxidized low-density lipoprotein-1 (Lox-1), and SR that binds phosphatidylserine and oxLDL (SR-PSOX/CXCL16) were examined. Four experimental groups were studied: sham and UUO male mice on either a high-fat Western diet or a control diet. Significantly more oxLDL accumulated in the tubulointerstitium of hypercholesterolemic mice compared with normocholesterolemic mice after 14 days of UUO (P < 0.01). Total kidney collagen was significantly higher in the obstructed kidneys of hypercholesterolemic mice compared with normocholesterolemic mice on day 14 (P < 0.01). After 14 days of obstruction, the number of interstitial F4/80+ macrophages and NF-kappaB activation increased in hypercholesterolemic mice compared with normocholesterolemic mice (P < 0.01). In normal kidneys, CD36, SR-A, Lox-1, and CXCL16 were primarily localized to renal tubular epithelia. After ureteral obstruction, CD36 increased at day 7; SR-A and Lox-1 progressively decreased in a time-dependent manner; and CXCL16 increased significantly with the onset of obstruction (P < 0.01). Strong tubular expression suggests that in addition to inflammatory interstitial cells, renal tubular scavenger receptors may help to orchestrate the inflammatory and fibrogenic pathways that are activated by oxLDL.
authors.affiliation: Children's Hospital and Regional Medical Center, Department of Pediatrics, University of Washington, 4800 Sand Point Way NE, Seattle WA 98015, USA. daryl.okamura@seattlechildrens.org
authors.forename: Daryl M
authors.initials: DM
authors.lastname: Okamura
authors.forename: Jesús M
authors.initials: JM
authors.lastname: López-Guisa
authors.forename: Katie
authors.initials: K
authors.lastname: Koelsch
authors.forename: Sarah
authors.initials: S
authors.lastname: Collins
authors.forename: Allison A
authors.initials: AA
authors.lastname: Eddy
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D015152:Blotting, Northern; D015153:Blotting, Western; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004036:Diet, Atherogenic; D005355:Fibrosis / Q000473:pathology; D006937:Hypercholesterolemia / Q000097:blood; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000473:pathology*; D017463:Receptors, Complement 3b / Q000502:physiology; D051131:Receptors, Oxidized LDL / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism / Q000502:physiology*; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000503:physiopathology
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D017463:Receptors, Complement 3b; D051131:Receptors, Oxidized LDL; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D003094:Collagen; D000594:Amino Acid Oxidoreductases; C482019:Loxl1 protein, mouse