Allison Eddy
Last active: 2/3/2012

Atherogenic scavenger receptor modulation in the tubulointerstitium in response to chronic renal injury.

Okamura DM, López-Guisa JM, Koelsch K, Collins S, Eddy AA
Am J Physiol Renal Physiol. 2007 293 (2): F575-85

PMID: 17537985 · DOI:10.1152/ajprenal.00063.2007

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.

MeSH Terms (27)

Amino Acid Oxidoreductases Animals Atherosclerosis Blotting, Northern Blotting, Western Chemokine CXCL6 Chemokine CXCL16 Chemokines, CXC Collagen Diet, Atherogenic Fibrosis Hypercholesterolemia Immunohistochemistry Kidney Kidney Failure, Chronic Lipoproteins, LDL Macrophages Male Mice Mice, Inbred C57BL Nephritis, Interstitial NF-kappa B Receptors, Complement 3b Receptors, Oxidized LDL Receptors, Scavenger Scavenger Receptors, Class A Ureteral Obstruction

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