A High Glucose Concentration Stimulates the Expression of Monocyte Chemotactic Peptide 1 in Human Mesangial Cells

Ihm, Chun Gyoo; Park, Jae Kyung; Hong, Seong Yeon; Lee, Tae Won; Cho, Byoung Soo; Kim, Myung Jae; Ryong, Dae; Ha, Hunjoo

doi:10.1159/000044988

Cited by 93 publications

(62 citation statements)

References 27 publications

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“…Our data provide evidence that the combined exposure to high glucose and stretch enhances MCP-1 production even further in this cell type. This is consistent with previous reports showing that high glucose upregulates MCP-1 in mesangial cells (10,39) and suggests that both metabolic and hemodynamic abnormalities, to which mesangial cells are exposed in vivo in the diabetic glomerulus, may contribute to the local increase in MCP-1.…”

Section: Discussionsupporting

confidence: 93%

“…Mesangial cell stretching activated NF-B via this classical pathway as we observed a 2.8-fold increase in phospho-Ser32/36-IB␣ levels. In mesangial cells, both PKC and protein tyrosine kinases (PTK) are intracellular mediators of stretch, and high glucose-induced MCP-1 expression is PKC dependent (10,23,39). However, in this work, neither calphostin C nor herbimycin A altered stretch-induced MCP-1 production, indicating that this effect was PKC-and PTK-independent.…”

Section: Discussioncontrasting

confidence: 55%

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Mechanical Stretch Induces Monocyte Chemoattractant Activity via an NF-κB-Dependent Monocyte Chemoattractant Protein-1-Mediated Pathway in Human Mesangial Cells

Gruden¹,

Setti²,

Hayward³

et al. 2005

Journal of the American Society of Nephrology

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Hemodynamic abnormalities are important in the pathogenesis of the glomerular damage in diabetes. Glomerular macrophage infiltration driven by the chemokine monocyte chemoattractant protein-1 (MCP-1) is an early event in diabetic nephropathy. The thiazolidinedione rosiglitazone ameliorates albumin excretion rate in diabetic patients with microalbuminuria and has anti-inflammatory properties, raising the possibility of a relationship between its renoprotective and anti-inflammatory activity. Investigated was whether mesangial cell stretching, mimicking in vitro glomerular capillary hypertension, enhances MCP-1 expression and monocyte chemoattractant activity. The effect of the combination of stretch with high glucose on MCP-1 production was studied and, finally, the effect of rosiglitazone on these processes was assessed. Stretching of human mesangial cells significantly enhanced their monocyte chemoattractant activity. This effect was mediated by MCP-1 as it was paralleled by a significant rise in both MCP-1 mRNA and protein levels and was completely abolished by MCP-1 blockade. Combined exposure to both stretch and high glucose further increased MCP-1 production. Stretch activated the IB-NF-B pathway, and NF-B inhibition, with the use of the specific inhibitor SN50, completely abolished stretch-induced MCP-1, indicating that stretch-induced MCP-1 was NF-B dependent. The addition of rosiglitazone significantly diminished stretch-induced NF-B activation, MCP-1 production, and monocyte chemotaxis. In conclusion, stretching of mesangial cells stimulates their monocyte chemoattractant activity via an NF-B-mediated, MCP-1-dependent pathway, and this effect is prevented by rosiglitazone.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 55%

Mechanical Stretch Induces Monocyte Chemoattractant Activity via an NF-κB-Dependent Monocyte Chemoattractant Protein-1-Mediated Pathway in Human Mesangial Cells

Gruden¹,

Setti²,

Hayward³

et al. 2005

Journal of the American Society of Nephrology

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“…However, human and rodent mesangial cells can synthesize MCP-1 in response to several factors that are thought to be involved in glomerular injury, such as interleukin-1, TNF-α, and low-density lipoprotein [19]. In the case of human mesangial cells, high concentration of glucose as well as glycated albumin have been reported to promote MCP-1 production [20,21].…”

Section: Discussionmentioning

confidence: 99%

Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model

et al. 2003

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Aims/hypothesis. We investigated the effect of cerivastatin, a statin, on the development of diabetic nephropathy in spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes. Methods. Diabetic SHR were given standard chow or chow containing cerivastatin at a dose of 0.1 mg/kg or 1.0 mg/kg for 12 weeks. Effects of cerivastatin on urinary albumin excretion, mesangial expansion, glomerular macrophage infiltration, and the number of anionic sites on the glomerular basement membrane (GBM) were assessed. Results. Cerivastatin did not affect the blood glucose concentration, blood pressure or serum cholesterol concentration in diabetic SHR. However, cerivastatin treatment caused a dose-dependent decrease of albuminuria and hyperfiltration. At 1.0 mg/kg, cerivastatin inhibited the diabetes-induced expansion of mesangial and tuft areas on histological examination of the kidneys, as well as the loss of anionic sites from the GBM evaluated with polyetyleneimine and the intraglomerular infiltration of ED1-positive macrophages evaluated by immunohistochemistry. Whole-kidney expression of mRNA for MCP-1 and TGF-β, estimated by the real-time quantitative RT-PCR, was increased (both 2.6-fold) in untreated diabetic SHR at 12 weeks. Cerivastatin treatment (1.0 mg/kg) inhibited the up-regulated expression of MCP-1 and TGF-β mRNA (decreased to 48% and 34%, respectively) in diabetic SHR. Conclusion/interpretation. In this hypertensive model of diabetic nephropathy, cerivastatin decreased albuminuria through suppression of glomerular hyperfiltration, mesangial expansion, and the loss of charge barrier independently of a cholesterol-lowering effect. These preventive effects could be at least partly due to inhibition of macrophage recruitment and activation, and inhibition of TGF-β overexpression. [Diabetologia (2003) 46:843-851]

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“…[13][14][15] In fact, CCL2 is expressed by human mesangial cells exposed to either high glucose concentrations or advanced glycation end products. 16,17 CCL2 is involved in the complex multistep process of leukocyte recruitment from intravascular to extravascular compartments, ie, glomeruli and the renal interstitium. 18 In fact, macrophage infiltrates are a common finding in human and experimental glomerulosclerosis and tubulointerstitial injury.…”

mentioning

confidence: 99%

Late Onset of Ccl2 Blockade with the Spiegelmer mNOX-E36–3′PEG Prevents Glomerulosclerosis and Improves Glomerular Filtration Rate in db/db Mice

Ninichuk¹,

Clauß²,

Kulkarni³

et al. 2008

The American Journal of Pathology

125

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Diabetic kidney disease is associated with monocyte chemoattractant CC chemokine ligand 2 (CCL2)-dependent glomerular and interstitial macrophage recruitment. In addition, nephropathy is delayed in Ccl2 mutant diabetic mice. However, whether the late onset of therapeutic Ccl2 blockade modulates the progression of advanced diabetic nephropathy remains unknown. We addressed this question by antagonizing Ccl2 with mNOX-E36 -3PEG, an anti-Ccl2 L-enantiomeric RNA aptamer (ie, a Spiegelmer), which binds murine Ccl2 and blocks the recruitment of ex vivo-labeled macrophages to the kidneys of db/db mice with type 2 diabetes. We injected mNOX-E36 -3PEG subcutaneously at a dose of 50 mg/kg three times per week into uninephrectomized (1K) db/db mice with advanced glomerulopathy from 4 to 6 months of age. mNOX-E36 -3PEG reduced the number of glomerular macrophages by 40% compared with nonfunctional (control) Spiegelmertreated 1K db/db mice. This result was associated with protection from diffuse glomerulosclerosis and significantly improved the glomerular filtration rate. mNOX-E36 -3PEG also reduced renal Ccl2 mRNA and protein expression compared with control Spiegelmer-treated 1K db/db mice of the same age. Together, the late onset of therapeutic Ccl2 blockade, eg, with specific Spiegelmers, offers protection from diffuse glomerulosclerosis in type 2 diabetic db/db mice and, thus, may represent a novel therapeutic strategy for advanced glomerulosclerosis.

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A High Glucose Concentration Stimulates the Expression of Monocyte Chemotactic Peptide 1 in Human Mesangial Cells

Cited by 93 publications

References 27 publications

Mechanical Stretch Induces Monocyte Chemoattractant Activity via an NF-κB-Dependent Monocyte Chemoattractant Protein-1-Mediated Pathway in Human Mesangial Cells

Mechanical Stretch Induces Monocyte Chemoattractant Activity via an NF-κB-Dependent Monocyte Chemoattractant Protein-1-Mediated Pathway in Human Mesangial Cells

Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model

Late Onset of Ccl2 Blockade with the Spiegelmer mNOX-E36–3′PEG Prevents Glomerulosclerosis and Improves Glomerular Filtration Rate in db/db Mice

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