Macrophage scavenger receptor-a-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation

Diabetes. 2007 Feb;56(2):363-72. doi: 10.2337/db06-0359.


Microinflammation is a common major mechanism in the pathogenesis of diabetic vascular complications, including diabetic nephropathy. Macrophage scavenger receptor-A (SR-A) is a multifunctional receptor expressed on macrophages. This study aimed to determine the role of SR-A in diabetic nephropathy using SR-A-deficient (SR-A(-/-)) mice. Diabetes was induced in SR-A(-/-) and wild-type (SR-A(+/+)) mice by streptozotocin injection. Diabetic SR-A(+/+) mice presented characteristic features of diabetic nephropathy: albuminuria, glomerular hypertrophy, mesangial matrix expansion, and overexpression of transforming growth factor-beta at 6 months after induction of diabetes. These changes were markedly diminished in diabetic SR-A(-/-) mice, without differences in blood glucose and blood pressure levels. Interestingly, macrophage infiltration in the kidneys was dramatically decreased in diabetic SR-A(-/-) mice compared with diabetic SR-A(+/+) mice. DNA microarray revealed that proinflammatory genes were overexpressed in renal cortex of diabetic SR-A(+/+) mice and suppressed in diabetic SR-A(-/-) mice. Moreover, anti-SR-A antibody blocked the attachment of monocytes to type IV collagen substratum but not to endothelial cells. Our results suggest that SR-A promotes macrophage migration into diabetic kidneys by accelerating the attachment to renal extracellular matrices. SR-A may be a key molecule for the inflammatory process in pathogenesis of diabetic nephropathy and a novel therapeutic target for diabetic vascular complications.

MeSH terms

  • Albuminuria
  • Animals
  • Collagen Type IV / metabolism
  • Creatinine / urine
  • Diabetes Mellitus, Experimental
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Gene Expression
  • Glycation End Products, Advanced / metabolism
  • Inflammation / genetics*
  • Kidney / metabolism*
  • Mice
  • Mice, Knockout
  • Osteopontin / metabolism
  • RNA, Messenger / metabolism
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class A / deficiency
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism*
  • Streptozocin
  • Transforming Growth Factor beta / metabolism


  • Collagen Type IV
  • Glycation End Products, Advanced
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Scavenger Receptors, Class A
  • Transforming Growth Factor beta
  • Osteopontin
  • Streptozocin
  • Creatinine