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- Title
Macrophage Scavenger Receptor-A-Deficient Mice Are Resistant Against Diabetic Nephropathy Through Amelioration of Microinflammation.
- Authors
Usui, Hitomi Kataoka; Shikata, Kenichi; Sasaki, Motofumi; Okada, Shinichi; Matsuda, Mitsuhiro; Shikata, Yasushi; Ogawa, Daisuke; Kido, Yuichi; Nagase, Ryo; Yozai, Kosuke; Ohga, Sakiko; Tone, Atsuhito; Wada, Jun; Takeya, Masahiro; Horiuchi, Seikoh; Kodama, Tatsuhiko; Makino, Hirofumi
- Abstract
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-β 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 micro-array 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. Diabetes 56:363-372, 2007
- Subjects
INFLAMMATION; DIABETIC angiopathies; VASCULAR diseases; DIABETIC nephropathies; DIABETES complications
- Publication
Diabetes, 2007, Vol 56, Issue 2, p363
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-0359