Receptor for advanced glycation end products mediates inflammation and enhanced expression of tissue factor in vasculature of diabetic apolipoprotein E-null mice

被引:227
作者
Kislinger, T
Tanji, N
Wendt, T
Qu, W
Lu, Y
Ferran, LJ
Taguchi, A
Olson, K
Bucciarelli, L
Goova, M
Hofmann, MA
Cataldegirmen, G
D'Agati, V
Pischetsrieder, M
Stern, DM
Schmidt, AM
机构
[1] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA
[2] Univ Erlangen Nurnberg, Abt Lebensmittelchem, Inst Pharm & Lebensmittelchem, Erlangen, Germany
关键词
receptor for advanced glycation end products glycation; diabetes; nephropathy; atherosclerosis;
D O I
10.1161/01.ATV.21.6.905
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Advanced glycation end products (AGEs) and their cell surface receptor, RAGE, have been implicated in the pathogenesis of diabetic complications. Here, we studied the role of RAGE and expression of its proinflammatory ligands, EN-RAGEs (S100/calgranulins), in inflammatory events mediating cellular activation in diabetic tissue. Apolipoprotein E-null mice were rendered diabetic with streptozotocin at 6 weeks of age. Compared with nondiabetic aortas and kidneys, diabetic aortas and kidneys displayed increased expression of RAGE, EN-RAGEs, and 2 key markers of vascular inflammation, vascular cell adhesion molecule (VCAM)-1 and tissue factor. Administration of soluble RAGE, the extracellular domain of the receptor, or vehicle to diabetic mice for 6 weeks suppressed levels of VCAM-1 and tissue factor in the aorta, in parallel with decreased expression of RAGE and EN-RAGEs. Diabetic kidney demonstrated increased numbers of EN-RAGE-expressing inflammatory cells infiltrating the glomerulus and enhanced mRNA for transforming growth factor-beta, fibronectin, and alpha (1) (IV) collagen. In mice treated with soluble RAGE, the numbers of infiltrating inflammatory cells and mRNA levels for these glomerular cytokines and components of extracellular matrix were decreased. These data suggest that activation of RAGE primes cells targeted for perturbation in diabetic tissues by the induction of proinflammatory mediators.
引用
收藏
页码:905 / 910
页数:6
相关论文
共 37 条
  • [1] Bobryshev YV, 1999, ATHEROSCLEROSIS, V143, P451
  • [2] NATURAL INHIBITOR OF TRANSFORMING GROWTH-FACTOR-BETA PROTECTS AGAINST SCARRING IN EXPERIMENTAL KIDNEY-DISEASE
    BORDER, WA
    NOBLE, NA
    YAMAMOTO, T
    HARPER, JR
    YAMAGUCHI, Y
    PIERSCHBACHER, MD
    RUOSLAHTI, E
    [J]. NATURE, 1992, 360 (6402) : 361 - 364
  • [3] Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion
    Brand, K
    Page, S
    Rogler, G
    Bartsch, A
    Brandl, R
    Knuechel, R
    Page, M
    Kaltschmidt, C
    Baeuerle, PA
    Neumeier, D
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (07) : 1715 - 1722
  • [4] COLLINS T, 1993, LAB INVEST, V68, P499
  • [5] FUTURA T, 1993, AM J KIDNEY DIS, V21, P180
  • [6] Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation
    Bowman, M. A. Hofmann
    Heydemann, A.
    Gawdzik, J.
    Shilling, R. A.
    Camoretti-Mercado, B.
    [J]. CLINICAL AND EXPERIMENTAL ALLERGY, 2011, 41 (06) : 878 - 889
  • [7] Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions - Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy
    Horie, K
    Miyata, T
    Maeda, K
    Miyata, S
    Sugiyama, S
    Sakai, H
    de Strihou, CV
    Monnier, VM
    Witztum, JL
    Kurokawa, K
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (12) : 2995 - 3004
  • [8] N-epsilon-(carboxymethyl)lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction
    Ikeda, K
    Higashi, T
    Sano, H
    Jinnouchi, Y
    Yoshida, M
    Araki, T
    Ueda, S
    Horiuchi, S
    [J]. BIOCHEMISTRY, 1996, 35 (24) : 8075 - 8083
  • [9] Significance of serum S100 release after coronary artery bypass grafting
    Jönsson, H
    Johnsson, P
    Alling, C
    Westaby, S
    Blomquist, S
    [J]. ANNALS OF THORACIC SURGERY, 1998, 65 (06) : 1639 - 1644
  • [10] DIABETES AND CARDIOVASCULAR-DISEASE - FRAMINGHAM-STUDY
    KANNEL, WB
    MCGEE, DL
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1979, 241 (19): : 2035 - 2038