Osteopontin expression in acute renal allograft rejection

Alchi, Bassam; Nishi, Shinichi; Kondo, Daisuke; Kaneko, Yoshikatsu; Matsuki, Asako; Imai, Naofumi; Ueno, Mitsuhiro; Iguchi, Seitaro; Sakatsume, Minoru; Narita, Ichiei; Yamamoto, Tadashi; Gejyo, Fumitake

doi:10.1111/j.1523-1755.2005.00153.x

Cited by 50 publications

(34 citation statements)

References 40 publications

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“…*P < 0.05 and **P < 0.01. ,Mki67,Fga,Fgg,Krt8,Krt18, and Krt19, were selected as candidate biomarkers because (i) there was the strong evidence supporting their usefulness as nephrotoxicity biomarkers in rats and other species (Alchi et al, 2005., Davis et al, 2004Dieterich et al, 2009;Kharasch et al, 2006;Thukral et al, 2005;Wang et al, 2008) and (ii) these selected genes were considered to be biologically related to the gene categories, such as tissue remodeling, inflammatory responses, and cell growth. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

et al. 2012

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-The present study aimed to establish candidate biomarker genes for the early detection of nephrotoxicity in mice, with a particular focus on nephrotoxicity caused by polyene macrolides. Comprehensive gene expression changes were evaluated using microarrays in a mouse model in which acute nephrotoxicity was induced by amphotericin B deoxycholate, trade name Fungizone. The upregulated genes identified through microarray analysis of kidney tissue of Fungizone-treated mice included several genes that have been reported as nephrotoxicity biomarkers in rats, and 14 genes were selected as candidate nephrotoxicity biomarkers. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR. Expression of genes encoding kidney injury molecule 1, lipocalin 2, tissue inhibitor of metalloproteinase 1, and secreted phosphoprotein 1 was highly upregulated by Fungizone, nystatin, natamycin, amphotericin B methyl ester, and liposomal amphotericin B, and their area under the ROC curve values were more than 0.95. These genes were more sensitive at detecting nephrotoxicity than traditional clinical chemistry and histopathology parameters. This study provides novel evidence that these nephrotoxicity biomarker genes identified are translatable to mice, and that they are useful for early and sensitive detection of nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

et al. 2012

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“…5 Gene profiling experiments performed on acute and chronic glomerulonephritis 6,7 and transplant renal disease 8 also found Opn mRNA to be highly increased and that it was one of the top genes that predicted renal damage. 5,9 Similarly, gene array studies performed on isolated podocytes identified Opn as the gene with the highest increase in mRNA expression after sheer stress 10 ; however, the reports are conflicting as to whether Opn plays a role in murine autoimmune glomerulonephritis.…”

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confidence: 99%

The Role of Osteopontin in the Development of Albuminuria

Lorenzen¹,

Shah²,

Biser³

et al. 2008

Journal of the American Society of Nephrology

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“…28,30 Occupancy of ␣ v ␤ 3 integrins can decrease monocyte binding capacity to ICAM-1 and VCAM-1, which are up-regulated in acute allograft rejection. 21,49,51,54 We and others 17,32 have shown that tubular osteopontin expression is significantly enhanced in renal biopsies with acute rejection and could be correlated with interstitial macrophage infiltration and cell proliferation. Osteopontin is an extracellular matrix protein containing an RGD sequence, which can interact with at least three different ␣ v -containing integrins, ␣ v ␤ 1 , ␣ v ␤ 3 , and ␣ v ␤ 5 ; its migratory activity seems to depend on the presence of a functional ␣ v ␤ 3 on the cell surface.…”

Section: Discussionmentioning

confidence: 94%

“…15,16 Furthermore, ligands of ␣ v ␤ 3 integrin include osteopontin, fibronectin, fibrinogen, thrombospondin, von Willebrand factor, collagen, and matrix metalloproteinase (MMP)-2, which are also present in rejecting transplanted organs. [17][18][19] The recruitment of leukocytes from the blood into tissue is essential for the development and maintenance of inflammation in acute rejection and is regulated by a complex network of cytokines, chemokines, and adhesion molecules. 12,20 ␣ v ␤ 3 was found to promote monocyte migration, to be involved in neutrophil mobility on extracellular matrix substrates in vitro, and leukocyte migration across the mesenteric endothelium in vivo.…”

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confidence: 99%

Anti-Inflammatory Effects of αv Integrin Antagonism in Acute Kidney Allograft Rejection

Bedke

Kiss

Behnes

et al. 2007

The American Journal of Pathology

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Integrin-mediated cell adhesion and signaling is essential to vascular development and inflammatory processes. Elevated expression of integrin ␣ v ␤ 3 has been detected in ischemia-reperfusion injury and rejecting heart allografts. We thus hypothesized that the inhibition of ␣ v -associated integrins may have potent antiinflammatory effects in acute kidney allograft rejection. We studied the effects of a peptidomimetic antagonist of ␣ v integrins in two rat models of renal allotransplantation, differing in degree of major histocompatibility complex mismatch. Integrin ␣ v ␤ 3 was up-regulated in rejecting renal allografts. Integrin antagonist reduced the histological signs of acute rejection, the intensity of the mononuclear cell infiltration, and cell proliferation in the grafted kidneys. This could be correlated to a reduced leukocyte-endothelial interaction and an improved peritubular microcirculation observed by intravital microscopy. In vitro under laminar flow conditions, the arrest of monocytes to interleukin-1␤-activated endothelium was decreased. Furthermore, in co-culture models the proliferation and transmigration of monocytes/macrophages, endothelium, and fibroblasts induced by renal tubular epithelia was efficiently inhibited by ␣ v integrin antagonism. These data reveal an important role of this integrin subclass in leukocyte recruitment and development and maintenance of acute rejection; blockade of ␣ v integrins may provide a new therapeutic strategy to attenuate acute allograft rejection.

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Osteopontin expression in acute renal allograft rejection

Abstract: These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.

Cited by 50 publications

References 40 publications

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

The Role of Osteopontin in the Development of Albuminuria

Anti-Inflammatory Effects of αv Integrin Antagonism in Acute Kidney Allograft Rejection

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