The Role of Osteopontin in the Development of Albuminuria

Lorenzen, Johan M.; Shah, Rajshree; Biser, Alisha; Staicu, Serban A.; Niranjan, T.G.; Garcı́a, Ana Maria; Gruenwald, Antje; Thomas, David B.; Shatat, Ibrahim F.; Supe, Katarine; Woroniecki, Robert P.; Suszták, Katalin

doi:10.1681/asn.2007040486

Cited by 82 publications

(88 citation statements)

References 24 publications

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“…15,16 Moreover, we and others have shown by DNA microarray studies that OPN gene expression is upregulated in the renal cortex and correlated with the degree of albuminuria in diabetic nephropathy, [16][17][18] suggesting that regulation of OPN expression could be a potential target for therapeutic intervention in diabetic nephropathy. Furthermore, albuminuria and renal damage are ameliorated in OPN-deficient diabetic mice, 19,20 also supporting the notion that OPN may be causally involved in the pathogenesis of diabetic nephropathy.…”

supporting

confidence: 58%

“…19 Furthermore, OPN deletion decreased albuminuria and the mesangial area in both type 1 (Ins2 Akita ) and type 2 (db/db) diabetic mouse models, and recombinant OPN upregulated TGF-b expression and signaling in cultured mouse mesangial cells. 20 In the present study, glomerular hypertrophy, mesangial matrix expansion, and macrophage infiltration were observed in the diabetic glomeruli, and these changes were ameliorated by administration of T0901317.…”

Section: Discussionmentioning

confidence: 95%

“…[12][13][14] Moreover, OPN deficiency prevents the development of diabetic nephropathy in murine models. 19,20 We recently reported that a peroxisome proliferator-activated receptor d agonist, GW0742, attenuates diabetic nephropathy by suppressing inflammatory mediators, including OPN and MCP-1. 35 Therefore, OPN is regarded as a key molecule in the pathogenesis of diabetic nephropathy, and it may be a potential therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

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Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy

Tachibana¹,

Ogawa

Matsushita³

et al. 2012

Journal of the American Society of Nephrology

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Osteopontin is a proinflammatory cytokine and monocyte chemoattractant implicated in the pathogenesis of diabetic nephropathy. Synthetic agonists for liver X receptors (LXRs) suppress the expression of proinflammatory genes, including osteopontin, but whether LXR activation modulates diabetic nephropathy is unknown. We administered the LXR agonist T0901317 to mice with streptozotocin-induced diabetes and evaluated its effects on diabetic nephropathy. The LXR agonist decreased urinary albumin excretion without altering blood glucose levels and substantially attenuated macrophage infiltration, mesangial matrix accumulation, and interstitial fibrosis. LXR activation suppressed the gene expression of inflammatory mediators, including osteopontin, in the kidney cortex. In vitro, LXR activation suppressed osteopontin expression in proximal tubular epithelial cells by inhibiting AP-1-dependent transcriptional activation of the osteopontin promoter. Taken together, these results suggest that inhibition of renal osteopontin by LXR agonists may have therapeutic potential for diabetic nephropathy.

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supporting

confidence: 58%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy

Tachibana¹,

Ogawa

Matsushita³

et al. 2012

Journal of the American Society of Nephrology

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“…Osteopontin has been identified as a marker of mesangial expansion in the diabetic mouse kidney [29], the severity of diabetic nephropathy in patients [30] and development of atherosclerosis [31]. The decrease in osteopontin expression with avosentan treatment is therefore consistent with decreases in the expression of genes encoding AT1a, TGF-β and NF-κB p65 subunit, which stimulate and are stimulated by osteopontin [32].…”

Section: Discussionmentioning

confidence: 87%

The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice

Watson

Schumacher

et al. 2009

Diabetologia

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Aims/hypothesis There is convincing evidence that the endothelin system contributes to diabetic nephropathy and cardiovascular disease. This study aimed to assess the effects of the non-peptidergic endothelin receptor A (ETA) antagonist avosentan in a mouse model of accelerated diabetic nephropathy and atherosclerosis in comparison with the ACE inhibitor, quinapril.Methods Apolipoprotein E (Apoe) knockout (KO) mice (n=20 per group, five groups) were randomised to the following groups: non-diabetic controls and streptozotocininduced diabetic animals gavaged daily for 20 weeks with placebo, avosentan (high dose: 30 mg/kg, or low dose: 10 mg/kg) or quinapril (given in drinking water, 30 mg/kg). Results BP was unchanged by avosentan treatment but decreased with quinapril treatment. Diabetes-associated albuminuria was significantly attenuated by high-dose avosentan after 10 and 20 weeks of treatment. Diabetic animals showed a decreased creatinine clearance, which was normalised by avosentan treatment. In diabetic mice, high-dose avosentan treatment significantly attenuated the glomerulosclerosis index, mesangial matrix accumulation, glomerular accumulation of the matrix proteins collagen IV, and renal expression of genes encoding connective tissue growth factor, vascular endothelial growth factor, transforming growth factor β and nuclear factor κB (p65 subunit). Furthermore, high-dose avosentan treatment was also associated with reduced expression of the genes for ETA, ETB and angiotensin receptor 1. The renoprotective effects of avosentan were comparable or superior to those observed with quinapril. High-dose avosentan also significantly attenuated diabetes-associated aortic atherosclerosis in Apoe KO mice and reduced macrophage infiltration and aortic nitrotyrosine expression. Conclusions/interpretation This study demonstrates that ETA blockade with avosentan may provide an alternate therapeutic strategy for the treatment of diabetic micro-and macrovascular complications.

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“…Derici et al [50] identified an association between similar urinary proteins and disease activity in UC, however none of these have been conclusive. Similarly, Mishima et al [51] detected elevated plasma levels of osteopontin in IBD patients, whilst Lorenzen et al [52] suggested a possible association between increased urinary osteopontin expression and steroid induced nephrotic syndrome. Whilst the relation between medications and their effect on protein expression is currently unclear, there are a number of implications in the context of biomarker discovery.…”

Section: Fecal Calprotectinmentioning

confidence: 97%

Current application of proteomics in biomarker discovery for inflammatory bowel disease

Chan¹,

Wasinger²,

Leong³

2016

WJGP

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Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease (IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD.

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The Role of Osteopontin in the Development of Albuminuria

Cited by 82 publications

References 24 publications

Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy

Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy

The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice

Current application of proteomics in biomarker discovery for inflammatory bowel disease

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