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

Hitomi Kataoka Usui, Kenichi Shikata, Motofumi Sasaki, Shinichi Okada, Mitsuhiro Matsuda, Yasushi Shikata, Daisuke Ogawa, Yuichi Kido, Ryo Nagase, Kosuke Yozai, Sakiko Ohga, Atsuhito Tone, Jun Wada, Motohiro Takeya, Seikoh Horiuchi, Tatsuhiko Kodama, Hirofumi Makino

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67 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)363-372
Number of pages10
JournalDiabetes
Volume56
Issue number2
DOIs
Publication statusPublished - Feb 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Usui, H. K., Shikata, K., Sasaki, M., Okada, S., Matsuda, M., Shikata, Y., Ogawa, D., Kido, Y., Nagase, R., Yozai, K., Ohga, S., Tone, A., Wada, J., Takeya, M., Horiuchi, S., Kodama, T., & Makino, H. (2007). Macrophage scavenger receptor-A-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation. Diabetes, 56(2), 363-372. https://doi.org/10.2337/db06-0359