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-κB 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

Galectin-3 preserves renal tubules and modulates extracellular matrix remodeling in progressive fibrosis

Renal tubular cell apoptosis is a critical detrimental event that leads to chronic kidney injury in association with renal fibrosis. The present study was designed to investigate the role of galectin-3 (Gal-3), an important regulator of multiple apoptotic pathways, in chronic kidney disease induced by unilateral ureteral obstruction (UUO). After UUO, Gal-3 expression significantly increased compared with basal levels reaching a peak increase of 95-fold by day 7. Upregulated Gal-3 is predominantly tubular at early time points after UUO but shifts to interstitial cells as the injury progresses. On day 14, there was a significant increase in TdT-mediated dUTP nick end labeling-positive cells (129%) and cytochrome c release (29%), and a decrease in BrdU-positive cells (62%) in Gal-3-deficient compared with wild-type mice. The degree of renal damage was more extensive in Gal-3-deficient mice at days 14 and 21, 35 and 21% increase in total collagen, respectively. Despite more severe fibrosis, myofibroblasts were significantly decreased by 58% on day 14 in the Gal-3-deficient compared with wild-type mice. There was also a corresponding 80% decrease in extracellular matrix synthesis in Gal-3-deficient compared with wild-type mice. Endo180 is a recently recognized receptor for intracellular collagen degradation that is expressed by interstitial cells during renal fibrogenesis. Endo180 expression was significantly decreased by greater than 50% in Gal-3-deficient compared with wild-type mice. Taken together, these results suggested that Gal-3 not only protects renal tubules from chronic injury by limiting apoptosis but that it may lead to enhanced matrix remodeling and fibrosis attenuation