CD36 regulates oxidative stress and inflammation in hypercholesterolemic CKD.

Okamura DM, Pennathur S, Pasichnyk K, López-Guisa JM, Collins S, Febbraio M, Heinecke J, Eddy AA
J Am Soc Nephrol. 2009 20 (3): 495-505

PMID: 19211715 · PMCID: PMC2653683 · DOI:10.1681/ASN.2008010009

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.

MeSH Terms (21)

Animals CD36 Antigens Chemokine CXCL10 Chemokines Fibroblasts Gene Expression Hypercholesterolemia Inflammation Kidney Lipoproteins Macrophages Male Mice Mice, Inbred C57BL Mice, Knockout NF-kappa B Oxidation-Reduction Oxidative Stress Renal Insufficiency, Chronic RNA, Messenger Transforming Growth Factor beta

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