TY - JOUR
T1 - Macrophage scavenger receptor-A-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation
AU - Usui, Hitomi Kataoka
AU - Shikata, Kenichi
AU - Sasaki, Motofumi
AU - Okada, Shinichi
AU - Matsuda, Mitsuhiro
AU - Shikata, Yasushi
AU - Ogawa, Daisuke
AU - Kido, Yuichi
AU - Nagase, Ryo
AU - Yozai, Kosuke
AU - Ohga, Sakiko
AU - Tone, Atsuhito
AU - Wada, Jun
AU - Takeya, Motohiro
AU - Horiuchi, Seikoh
AU - Kodama, Tatsuhiko
AU - Makino, Hirofumi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/2
Y1 - 2007/2
N2 - 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 (SRA -/-) 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 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.
AB - 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 (SRA -/-) 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 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.
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U2 - 10.2337/db06-0359
DO - 10.2337/db06-0359
M3 - Article
C2 - 17259380
AN - SCOPUS:33847078388
SN - 0012-1797
VL - 56
SP - 363
EP - 372
JO - Diabetes
JF - Diabetes
IS - 2
ER -
