Role of receptor for advanced glycation end-products and signalling events in advanced glycation end-product-induced monocyte chemoattractant protein-1 expression in differentiated mouse podocytes

Gu, Leyi; Hagiwara, Shinji; Fan, Qiuling; Tanimoto, Masuhisa; Kobata, Mami; Yamashita, M; Nishitani, Tomohito; Gohda, Tomohito; Ni, Zhaohui; Qian, Jiaqi; Horikoshi, Satoshi; Tomino, Yasuhiko

doi:10.1093/ndt/gfi210

Cited by 105 publications

(90 citation statements)

References 40 publications

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“…Among various liver enzymes, ALT is most closely related to liver fat accumulation, and consequently ALT has been used as a marker of nonalcoholic fatty liver in diabetes (29). We have recently found that D 1 3 ( 3 -4 ) 1 8 5 -1 8 9 (23)(24)(25)(26). Further, several reports show the positive correlaserum AGE levels are significantly elevated in patients with nonalcoholic steatohepatitis compared with simple steatosis or healthy control subjects, and that the AGE-RAGE interaction induces transforming growth factor-␤ in human cultured hepatic stellate cells (HSCs), promoting the transdifferentiation of HSCs to myofibroblasts and thereby being involved in the process of liver fibrosis (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of sRAGE, the Soluble Form of Receptor for Advanced Glycation End Products, Are Associated with Inflammatory Markers in Patients with Type 2 Diabetes

Nakamura

Yamagishi

Adachi

et al. 2007

Mol Med

124

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Advanced glycation end products (AGEs) and their receptor (RAGE) play an important role in accelerated atherosclerosis in diabetes. We have recently found that the soluble form of RAGE (sRAGE) levels are significantly higher in type 2 diabetic patients than in nondiabetic subjects and positively associated with the presence of coronary artery disease in diabetes. In this study, we examined whether serum levels of sRAGE correlated with inflammatory biomarkers in patients with type 2 diabetes. Eighty-six Japanese type 2 diabetic patients (36 men and 50 women, mean age 68.4 ± 9.6 years) underwent a complete history and physical examination, determination of blood chemistries, sRAGE, monocyte chemotactic protein-1 (MCP-1), adiponectin, tumor necrosis factor-␣ (TNF-␣), and interleukin-6 (IL-6). Univariate regression analysis showed that serum levels of sRAGE positively correlated with alanine aminotransferase (ALT) (r = 0.437, P = 0.0001), MCP-1 (r = 0.359, P = 0.001), TNF-␣ (r = 0.291, P = 0.006), and hyperlipidemia medication (r = 0.218, P = 0.044). After multiple regression analyses, ALT (P < 0.0001), MCP-1 (P = 0.007), and TNF-␣ (P = 0.023) remained significant. The present study demonstrates for the first time that serum levels of sRAGE are positively associated with MCP-1 and TNF-␣ levels in type 2 diabetic patients. These observations suggest the possibility that sRAGE level may become a novel biomarker of vascular inflammation in type 2 diabetic patients.

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Section: Discussionmentioning

confidence: 99%

Serum Levels of sRAGE, the Soluble Form of Receptor for Advanced Glycation End Products, Are Associated with Inflammatory Markers in Patients with Type 2 Diabetes

Nakamura

Yamagishi

Adachi

et al. 2007

Mol Med

124

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“…The presence of these compounds in renal structures may contribute to the tissue lesions described in diabetes, thus altering the architecture of the extra-cellular matrix through glycation reactions with the formation of protein cross links [28,123]. Another mechanism that appears to participate in the pathogenesis of nephropathy is also mediated by the AGEs through their interaction with the RAGEs [148], as well as by the deregulation of these receptors, particularly at the podocytes [57]. Indeed, a direct relationship between serum levels of circulating RAGEs and AGEs and the severity of the nephropathy in DM2 patients has been established [130].…”

Section: Ages and Chronic Diabetic Complicationsmentioning

confidence: 99%

Involvement of advanced glycation end products in the pathogenesis of diabetic complications: the protective role of regular physical activity

Magalhães

Appell

Duarte

2008

Eur Rev Aging Phys Act

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“…4 Monocyte chemoattractant protein-1 (MCP-1) is a potent mononuclear cell chemoattractant produced by a variety of mesenchymal cells, including glomerular cells. [5][6][7] Within the glomeruli, there is MCP-1 overexpression in both crescent GN 8 and nephrotic conditions. 9 -11 Furthermore, immunohistochemistry studies have shown that glomerular podocytes are the predominant glomerular cell type overexpressing MCP-1 in various proteinuric conditions, such as diabetic, hypertensive, and membranous nephropathies.…”

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confidence: 99%

The Monocyte Chemoattractant Protein-1/Cognate CC Chemokine Receptor 2 System Affects Cell Motility in Cultured Human Podocytes

Burt

Salvidio

Tarabra

et al. 2007

The American Journal of Pathology

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In crescentic glomerulonephritis (GN), monocyte chemoattractant protein-1 (MCP-1) is overexpressed within the glomeruli, and MCP-1 blockade has renoprotective effects. Adult podocytes are in a quiescent state, but acquisition of a migratory/proliferative phenotype has been described in crescentic GN and implicated in crescent formation. The cognate CC chemokine receptor 2 (CCR2), the MCP-1 receptor, is expressed by other cell types besides monocytes and has been implicated in both cell proliferation and migration. We investigated whether MCP-1 binding to CCR2 can induce a migratory/proliferative response in cultured podocytes. MCP-1 binding to CCR2 enhanced podocyte chemotaxis/haptotaxis in a concentration-dependent manner and had a modest effect on cell proliferation. Closure of a wounded podocyte monolayer was delayed by CCR2 blockade, and CCR2 was overexpressed at the wound edge, suggesting a role for CCR2 in driving podocyte migration. Immunohistochemical analysis of kidney biopsies from patients with crescentic GN demonstrated CCR2 expression in both podocytes and cellular crescents, confirming the clinical relevance of our in vitro findings. In conclusion, the MCP-1/CCR2 system is functionally active in podocytes and may be implicated in the migratory events triggered by podocyte injury in crescentic GN and other glomerular diseases. Podocytes are highly differentiated cells with a complex cellular morphology. The podocyte cell body bulges into the urinary space and gives rise to primary processes that extend toward the capillaries to which they affix by numerous foot processes. The foot process of neighboring podocytes interdigitate, leaving between them filtration slits bridged by an extracellular structure, known as the slit diaphragm, which represents the major restriction site to protein filtration. 1 In the adult kidney, podocytes are in a quiescent state; however, both proliferation and acquisition of a migratory phenotype have been reported in pathological conditions. In crescentic glomerulonephritis (GN), podocytes detach from the glomerular basement membrane (GBM), assume a migratory phenotype, and trigger crescent formation by establishing bridges between the tuft and the Bowman's capsule. 2 In addition, cells derived from migrated podocytes proliferate and participate in crescent formation. 3 Furthermore, in nephrotic conditions, podocyte effacement, which requires cytoskeleton remodeling, foot process movement over the GBM, and slit diaphragm reconstruction, may also be considered a migratory event aimed to compensate for podocyte loss by covering areas of bare GBM. 4 Monocyte chemoattractant protein-1 (MCP-1) is a potent mononuclear cell chemoattractant produced by a variety of mesenchymal cells, including glomerular cells. [5][6][7] Within the glomeruli, there is MCP-1 overexpression in both crescent GN 8 and nephrotic conditions. 9 -11 Furthermore, immunohistochemistry studies have shown that glomerular podocytes are the predominant glomerular cell type overexpressing MCP-1 in various prote...

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Role of receptor for advanced glycation end-products and signalling events in advanced glycation end-product-induced monocyte chemoattractant protein-1 expression in differentiated mouse podocytes

Abstract: These results suggest that AGEs and CML induce MCP-1 expression in podocytes through activation of RAGE and generation of intracellular ROS. NF-kappaB and Sp1 regulate MCP-1 gene transcription.

Cited by 105 publications

References 40 publications

Serum Levels of sRAGE, the Soluble Form of Receptor for Advanced Glycation End Products, Are Associated with Inflammatory Markers in Patients with Type 2 Diabetes

Serum Levels of sRAGE, the Soluble Form of Receptor for Advanced Glycation End Products, Are Associated with Inflammatory Markers in Patients with Type 2 Diabetes

Involvement of advanced glycation end products in the pathogenesis of diabetic complications: the protective role of regular physical activity

The Monocyte Chemoattractant Protein-1/Cognate CC Chemokine Receptor 2 System Affects Cell Motility in Cultured Human Podocytes

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