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Am J Physiol Renal Physiol (May 30, 2007). doi:10.1152/ajprenal.00063.2007
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Submitted on February 9, 2007
Accepted on May 25, 2007

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

Daryl M. Okamura1*, Jesus M. Lopez-Guisa2, Katie Koelsch2, Sarah J. Collins2, and Allison A. Eddy1

1 Nephrology, Children's Hospital & Regional Medical Center, Seattle, Washington, United States; Pediatrics, University of Washington, Seattle, Washington, United States
2 Nephrology, Children's Hospital & Regional Medical Center, Seattle, Washington, United States

* To whom correspondence should be addressed. E-mail: daryl.okamura{at}seattlechildrens.org.

Oxidized 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 oxidized lipoprotein (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 to normocholesterolemic mice after 14 days of UUO (P <0.01). Total kidney collagen was significantly higher in the obstructed kidneys of hypercholesterolemic mice compared to normocholesterolemic mice on day 14 (P <0.01). After 14 days of obstruction, the number of interstitial F4/80+ macrophages and NF-kappa-B activation increased in hypercholesterolemic mice compared to 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.







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