| First Author | Wang W | Year | 2012 |
| Journal | Kidney Int | Volume | 81 |
| Issue | 10 | Pages | 1002-14 |
| PubMed ID | 22377830 | Mgi Jnum | J:198185 |
| Mgi Id | MGI:5495629 | Doi | 10.1038/ki.2011.457 |
| Citation | Wang W, et al. (2012) Deletion of scavenger receptor A protects mice from progressive nephropathy independent of lipid control during diet-induced hyperlipidemia. Kidney Int 81(10):1002-14 |
| abstractText | Scavenger receptor A (SR-A) is a key transmembrane receptor in the endocytosis of lipids and contributes to the pathogenesis of atherosclerosis. To assess its role in hyperlipidemic chronic kidney disease, wild-type and SR-A-deficient (knockout) mice underwent uninephrectomy followed by either normal or high-fat diet. After 16 weeks of diet intervention, hyperlipidemic wild-type mice presented characteristic features of progressive nephropathy: albuminuria, renal fibrosis, and overexpression of transforming growth factor (TGF)-beta1/Smad. These changes were markedly diminished in hyperlipidemic knockout mice and attributed to reduced renal lipid retention, oxidative stress, and CD11c(+) cell infiltration. In vitro, overexpression of SR-A augmented monocyte chemoattractant protein-1 release and TGF-beta1/Smad activation in HK-2 cells exposed to oxidized low-density lipoprotein. SR-A knockdown prevented lipid-induced cell injury. Moreover, wild-type to knockout bone marrow transplantation resulted in renal fibrosis in uninephrectomized mice following 16 weeks of the high-fat diet. In contrast, knockout to wild-type bone marrow transplantation led to markedly reduced albuminuria, CD11c(+) cell infiltration, and renal fibrosis compared to wild-type to SR-A knockout or wild-type to wild-type bone marrow transplanted mice, without difference in plasma lipid levels. Thus, SR-A on circulating leukocytes rather than resident renal cells predominantly mediates lipid-induced kidney injury. |
