Increased expression of selectins in kidneys of patients with diabetic nephropathy

Hirata, Kyoji; Shikata, Kenichi; Matsuda, Mitsuhiro; Akiyama, Kenji; Sugimoto, Hikaru; Kushiro, Masahiko; Makino, Hírofumi

doi:10.1007/s001250050888

Cited by 102 publications

(81 citation statements)

References 19 publications

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“…This finding is consistent with previous observations of increased P-selectin expression in kidneys of patients with DN (Hirata et al 1998) and of upregulated human P-selectin gene expression due to NF-κ B activation (Pan and McEver 1995;Weyrich et al 1995). To our knowledge, this is the first in vivo study that suggests a correlation between DN and NF-κ B activation.…”

Section: Discussionsupporting

confidence: 92%

“…Such increases indicate that P-selectin protein accumulates the kidney of DN rats. This observation supports the finding of increased P-selectin expression in kidneys of patients with DN (Hirata et al 1998). We also demonstrated that the accumulation of P-selectin could be inhibited by administration of PDTC at 4 hours prior to the sacrifice, indicating that the accumulation in the renal cortex is caused by NF-κ B activation.…”

Section: Discussionsupporting

confidence: 91%

“…Many of these cytokines are produced by hematopoietic mononuclear cells including monocytes and macrophages, suggesting that infiltrating monocytes/macrophages in the kidney play a critical role in the development of chronic renal injury (Hofmann et al 1999). Furthermore, the accumulation in the kidney of adhesion molecules such as vascular cell adhesion molecule-1 (Seron et al 1991), intracellular adhesion molecule (ICAM)-1 (Sugimoto et al 1997), and P-selectin (Hirata et al 1998) may induce structural damage. P-selectin is expressed on activated endothelial cells and platelets (Geng et al 1990) and regulates the initial interactions between leukocytes and the blood vessel wall as well as between activated platelets and leukocytes (Vandendries et al 2004).…”

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confidence: 99%

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Nuclear Factor-.KAPPA.B Activation in Diabetic Rat Kidney: Evidence for Involvement of P-Selectin in Diabetic Nephropathy

Iwamoto

Mizuiri

Arita

et al. 2005

Tohoku J. Exp. Med.

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Activation of a transcription factor, nuclear factor-κ B (NF-κ B), is a key step in the pathogenesis of diabetic nephropathy. In this study, we investigated the role of P-selectin, a platelet-derived adhesion molecule, in diabetic nephropathy by examining the activation status of NF-κ B in the renal cortex of streptozotocin (STZ)-treated rats. The STZ treatment induced pathogenetic parameters such as increased creatinine clearance, increased blood glucose and massive albuminuria in a timedependent manner. Electrophoretic mobility shift assays (EMSAs) with a specific probe, representing the P-selectin gene promoter, revealed the activation status of NF-κ B in the STZ-treated rats, as judged by the time-dependent increase in the formation of the specific protein-DNA complexes. This increase was associated with the increased pathogenetic parameters. Supershift assays with specific antibodies revealed that p50, but not p52, p65, Rel B, or c-Rel, may be involved in the activation of NF-κ B, though the component primarily responsible for the increase could not be determined. Western blot analysis confirmed an increase in P-selectin in STZ-treated rats. Notably, treatment with ammonium pyrrolidinedithiocarbamate, an antioxidant and inhibitor of NF-κ B, inhibited the activation of NF-κ B in STZ-treated rats and decreased P-selectin in the renal cortical tissue. Our results indicate that expression of the P-selectin gene is induced through the activation of NF-κ B and that P-selectin may be involved in the pathogenesis of diabetic nephropathy. nuclear factor-κ B; P-selectin; diabetic nephropathy; rat; streptozotocin

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

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Nuclear Factor-.KAPPA.B Activation in Diabetic Rat Kidney: Evidence for Involvement of P-Selectin in Diabetic Nephropathy

Iwamoto

Mizuiri

Arita

et al. 2005

Tohoku J. Exp. Med.

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“…Leucocyte infiltration into inflammatory sites and atherosclerotic lesions is mediated by cell adhesion molecules and chemokines such as chemokine (C-C motif) ligand 2 (CCL2) (also known as monocyte chemoattractant protein-1). We have recently demonstrated in a series of studies [10][11][12] that intercellular adhesion molecule-1 (ICAM-1) is upregulated and mediates macrophage infiltration in diabetic kidney tissues. We have also shown that ICAM-1 deficiency protects against renal injuries after induction of diabetes using ICAM-1 knockout mice [13].…”

Section: Introductionmentioning

confidence: 99%

Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats

et al. 2005

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Aims/hypothesis: Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats. Methods: STZinduced diabetic rats were treated orally with erythromycin (5 mg/kg body weight) or vehicle every day for 8 weeks.To evaluate the effect of erythromycin treatment, we measured urinary albumin excretion, and examined the following in the kidney: histological changes, the expression of intercellular adhesion molecule-1 (ICAM-1), macrophage infiltration, and nuclear factor-kappa B (NF-κB) activity. Results: Erythromycin significantly reduced urinary albumin excretion without affecting blood glucose levels and blood pressure. Erythromycin also attenuated glomerular hypertrophy, mesangial expansion, macrophage infiltration and ICAM-1 expression in renal tissues. The expression of the gene encoding TGFB1 (also known as TGF-β1), type IV collagen protein production and NF-κB activity in renal tissues were increased in diabetic rats and reduced by erythromycin treatment. Conclusions/ interpretation: Erythromycin prevented renal injuries without changes of blood glucose levels and blood pressure in experimental diabetic rats. These results suggest that the renoprotective effects of erythromycin are based on its anti-inflammatory effect via suppression of NF-κB activation. Modulation of microinflammation with erythromycin may provide a new approach for diabetic nephropathy.

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“…Blocking antibodies against ICAM-1 prevent leukocyte influx into the glomeruli and renal injury in experimental glomerulonephritis (7,8) and renal ablation models (9). We previously (11) demonstrated the accumulation of macrophages and increased expression of cell adhesion molecules, such as ICAM-1 and selectins, in the kidneys of patients with diabetic nephropathy. Furthermore, we reported (12) that the upregulation of ICAM-1 associated with macrophage infiltration occurs in very early stages, soon after the induction of diabetes, and is maintained throughout the observation period in streptozotocin (STZ)-induced diabetic rats.…”

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confidence: 99%

Intercellular Adhesion Molecule-1–Deficient Mice Are Resistant Against Renal Injury After Induction of Diabetes

et al. 2003

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Increased expression of selectins in kidneys of patients with diabetic nephropathy

Cited by 102 publications

References 19 publications

Nuclear Factor-.KAPPA.B Activation in Diabetic Rat Kidney: Evidence for Involvement of P-Selectin in Diabetic Nephropathy

Nuclear Factor-.KAPPA.B Activation in Diabetic Rat Kidney: Evidence for Involvement of P-Selectin in Diabetic Nephropathy

Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats

Intercellular Adhesion Molecule-1–Deficient Mice Are Resistant Against Renal Injury After Induction of Diabetes

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