CD36 regulates oxidative stress and inflammation in hypercholesterolemic CKD.
Scavenger receptors play a central role in atherosclerosis by processing oxidized lipoproteins and mediating their cellular effects. Recent studies suggested that the atherogenic state correlates with progression of chronic kidney disease (CKD); therefore, scavenger receptors are candidate mediators of renal fibrogenesis. Here, we investigated the role of CD36, a class B scavenger receptor, in a hypercholesterolemic model of CKD. We placed CD36-deficient mice and wild-type male mice on a high-fat Western diet for 7 to 8 wk and then performed either sham or unilateral ureteral obstruction surgery. CD36-deficient mice developed significantly less fibrosis compared with wild-type mice at days 3, 7, and 14 after obstruction. Compared with wild-type mice, CD36-deficient mice had significantly more interstitial macrophages at 7 d but not at 14 d. CD36-deficient mice exhibited reduced levels of activated NF-kappaB and oxidative stress (assessed by measuring fatty acid-derived hydroxyoctadecadienoic acid and protein carbonyl content) and decreased accumulation of interstitial myofibroblasts compared with wild-type mice. These data suggest that CD36 is a key modulator of proinflammatory and oxidative pathways that promote fibrogenesis in CKD.
Okamura
Daryl M
DM
Department of Pediatrics, Seattle Children's Research Institute, Division of Nephrology, Seattle, WA 98105, USA. daryl.okamura@seattlechildrens.org
Pennathur
Subramaniam
S
Pasichnyk
Katie
K
López-Guisa
Jesús M
JM
Collins
Sarah
S
Febbraio
Maria
M
Heinecke
Jay
J
Eddy
Allison A
AA
D000818:Animals; D018955:CD36 Antigens / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054357:Chemokine CXCL10 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics; D005347:Fibroblasts / Q000473:pathology; D015870:Gene Expression; D006937:Hypercholesterolemia / Q000150:complications* / Q000503:physiopathology*; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D018955:CD36 Antigens; D054357:Chemokine CXCL10; D018925:Chemokines; C485433:Cxcl10 protein, mouse; D008074:Lipoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta