Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes

被引:262
作者
Okada, S [1 ]
Shikata, K [1 ]
Matsuda, M [1 ]
Ogawa, D [1 ]
Usui, H [1 ]
Kido, Y [1 ]
Nagase, R [1 ]
Wada, J [1 ]
Shikata, Y [1 ]
Makino, H [1 ]
机构
[1] Okayama Univ, Grad Sch Med & Dent, Dept Med & Clin Sci, Okayama 7008558, Japan
关键词
D O I
10.2337/diabetes.52.10.2586
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression. of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.
引用
收藏
页码:2586 / 2593
页数:8
相关论文
共 39 条
[1]  
ADLER S, 1994, J AM SOC NEPHROL, V5, P1165
[2]  
Bullard DC, 1997, J IMMUNOL, V159, P2058
[3]   Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes [J].
Coimbra, TM ;
Janssen, U ;
Gröne, HJ ;
Ostendorf, T ;
Kunter, U ;
Schmidt, H ;
Brabant, G ;
Floege, J .
KIDNEY INTERNATIONAL, 2000, 57 (01) :167-182
[4]   P-selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice [J].
Collins, RG ;
Velji, R ;
Guevara, NV ;
Hicks, MJ ;
Chan, L ;
Beaudet, AL .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (01) :189-194
[5]   A new class of obesity genes encodes leukocyte adhesion receptors [J].
Dong, ZM ;
GutierrezRamos, JC ;
Coxon, A ;
Mayadas, TN ;
Wagner, DD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) :7526-7530
[6]   THE ROLE OF MACROPHAGES IN DIABETIC GLOMERULOSCLEROSIS [J].
FURUTA, T ;
SAITO, T ;
OOTAKA, T ;
SOMA, J ;
OBARA, K ;
ABE, K ;
YOSHINAGA, K .
AMERICAN JOURNAL OF KIDNEY DISEASES, 1993, 21 (05) :480-485
[7]   Increased expression of selectins in kidneys of patients with diabetic nephropathy [J].
Hirata, K ;
Shikata, K ;
Matsuda, M ;
Akiyama, K ;
Sugimoto, H ;
Kushiro, M ;
Makino, H .
DIABETOLOGIA, 1998, 41 (02) :185-192
[8]  
Janssen U, 1998, J AM SOC NEPHROL, V9, P1805
[9]   Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats [J].
Kato, S ;
Luyckx, VA ;
Ots, M ;
Lee, KW ;
Ziai, F ;
Troy, JL ;
Brenner, BM ;
Mackenzie, HS .
KIDNEY INTERNATIONAL, 1999, 56 (03) :1037-1048
[10]  
KAWASAKI K, 1993, J IMMUNOL, V150, P1074