Renal Effects of Coxsackie B4 Virus in Hyper-IgA Mice

Kawasaki, Yukihiko; Isome, Masato; Nozawa, Ruriko; Suzuki, Hitoshi

doi:10.1681/asn.2006050495

Cited by 14 publications

(10 citation statements)

References 18 publications

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“…*P Ͻ 0.05; **P Ͻ 0.01. 29 reported that viral infection can provoke renal injury also in murine IgAN. For assessment of potential influence of exogenous pathogens on the disease progression, the IgAN-prone ddY mice were maintained separately under the conventional and SPF conditions in this study.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 9 Affects Severity of IgA Nephropathy

Suzuki

Narita

et al. 2008

Journal of the American Society of Nephrology

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164

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Environmental pathogens are suspected to aggravate renal injury in IgA nephropathy (IgAN), but neither underlying mechanisms nor specific exogenous antigens have been identified. In this study, a genome-wide scan of ddY mice, which spontaneously develop IgAN, was performed, and myeloid differentiation factor 88 (MyD88) was identified as a candidate gene for progression of renal injury ( 2 ϭ 21.103, P ϭ 0.00017). For evaluation of the potential influence of environmental pathogens on progression of renal injury, ddY mice were housed in either conventional or specific pathogen-free conditions. Expression of genes encoding toll-like receptors (TLR) and the signaling molecule MyD88 were quantified by real-time reverse transcription-PCR in splenocytes. Although the housing conditions did not affect the prevalence of IgAN, the severity of renal injuries was higher in the conventionally housed group. Mice that had IgAN and were housed in conventional conditions had higher levels of TLR9 and MyD88 transcripts than mice that had IgAN and were housed in specific pathogen-free conditions. Furthermore, nasal challenge with CpG-oligodeoxynucleotides, which are ligands for TLR9, aggravated renal injury, led to strong Th1 polarization, and increased serum and mesangial IgA. For investigation of whether these results may be generalizable to humans, single-nucleotide polymorphisms in the TLR9 and MyD88 genes were analyzed in two cohorts of patients with IgAN; an association was observed between TLR9 polymorphisms and disease progression. In summary, these findings suggest that activation of the TLR9/MyD88 pathway by common antigens may affect the severity of IgAN.

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Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 9 Affects Severity of IgA Nephropathy

Suzuki

Narita

et al. 2008

Journal of the American Society of Nephrology

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164

153

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“…The immunoperoxidase staining for α-SMA, PCNA, VEGF, Ang-1, and CD31 was evaluated using the methods previously described by Kawasaki et al [18,19]. Primary antibodies included mouse anti-human α-SMA (1A4; Dako, Glostrup, Denmark), mouse anti-human PCNA (19A2; Coulter, Hialeah, Fla., USA), goat anti-mouse VEGF (RM0008-6572; NOV) monoclonal antibodies, rabbit anti-mouse Ang-1 (Anti-AUGPT1; LSB), and rabbit anti-mouse CD31 (ER-MP12; BMA) polyclonal antibodies were used for IHM.…”

Section: Methodsmentioning

confidence: 99%

Role of Vascular Endothelial Growth Factor and Angiopoietin 1 in Renal Injury in Hemolytic Uremic Syndrome

Ohara¹,

Kawasaki²,

Abe³

et al. 2012

Am J Nephrol

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Background/Aims: The recovery process from renal injury in hemolytic uremic syndrome (HUS) remains obscure. In order to clarify the role of vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) in the renal recovery from HUS, we produced a model of mild HUS and examined the renal recovery process. Methods: We investigated three groups of mice. Group 1 consisted of mice that received an injection of Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS); group 2 consisted of mice that received an injection of low dose of Stx2 and LPS, and group 3 consisted of control mice. Results: Serum Cr levels in group 1 were greater than those in group 2, and all mice in group 1 died, whereas all mice in group 2 remained alive. Endothelial injury at 24 h in group 1 was higher than in group 2. Electron-microscopic findings demonstrated that the endothelial cells formed immature capillary-like lumina from 7 to 28 days with increases in the expression of CD31-positive cells. Glomerular VEGF expression decreased at 72 h in group 1, but gradually increased in group 2. Glomerular Ang-1 expression peaked from 72 h to 28 days. Ang-1 expression was frequently found in the endothelial cell region of vesicle walls simultaneous with increased CD31-positive staining. Conclusion: Our findings suggest that VEGF and Ang-1 play important roles in the recovery process, particularly in the regeneration of endothelial injury.

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“…In many of these systems, genetic proclivity for altered systemic immunity is recognized and likely explains the predominance of IgAN [49][50][51]. However, in some instances, the known parameters of the immune response would not necessarily predict predilection for a strong IgA response or alterations in immunoregulation; nonetheless, strong serum IgA responses and IgA predominance or co-dominance in a subsequent glomerulonephritis is observed [68][69][70][71][72]. The antigens in these systems are bacterial or viral pathogens that might invoke innate immunity, which modulates the adaptive antibody response through mechanisms that are currently being elucidated (see 'T Cell Regulation and Cytokine Polarity' , below).…”

Section: Generation Of Iga By Extramucosal (Systemic) Immunizationmentioning

confidence: 99%

“…Indeed, co-stimulation with 'superantigen' , vaccination of selected strains of rodents predisposed towards an immune response favoring IgA production and/or Th2 cytokine profiles, or immunomodulation by innate responses can also lead to IgAN [33,36,[49][50][51][68][69][70][71][72]. In addition, very intense cognate responses can drive immune responses with specificity for elements that are not a component of the intense stimulus, which is especially true for simpler antigens, those that resemble commensals or pathogens, or those that are prevalent in the environment in which the host survives.…”

Section: Polyclonal Activation and Dysregulated Ig Productionmentioning

confidence: 99%

“…These experiments cannot discriminate indirect effects of innate responses of circulating leukocytes from direct effects due to innate responses of indigenous glomerular cells. Contributions of both extrarenal effects introduced by exogenous cytokines [135] and intrarenal effects of innate responses [136] are recognized, and may underlie exacerbation of IgAN by pathogens [68][69][70][71][72]. Although innate responses can shape adaptive immunity, the recently reported effects of pathogen-derived DNA on the ddY model of IgAN appear to represent intrarenal effects that do not stem from immunomodulation [137].…”

Section: Other Co-depositsmentioning

confidence: 99%

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Prospects and Perspectives on IgA Nephropathy from Animal Models

Emancipator

2011

Contributions to Nephrology

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The focus of this chapter is a systematic and critical review of the insights that experimental models have contributed to our understanding of IgA nephropathy (IgAN). We consider the generation of IgA subject to glomerular deposition, the partitioning of IgA between the circulation and glomeruli, the clearance of IgA and complexes containing IgA from the circulation, the 'upstream' effectors of glomerular pathophysiology, the inflammatory mediators that connect intraglomerular stimuli to functional and morphologic effects, and the contribution of animal models to our current understanding of the role that glycosylation of IgA plays in the genesis of IgAN. In each of these subsections, the evidence in favor of each principle or hypothesis is weighed in consideration of other potentially contradictory evidence and relevant issues related to IgAN in patients. The key limitations of each model system are presented, and where possible, reconciliation of discrepant observations are proposed. Subsequently, a synopsis of spontaneous models that do not offer particular mechanistic insights, and a compilation of experimental therapeutic initiatives, are reviewed. In all respects, the discussion of observations in patients or cells in vitro is limited to points where these data impinge upon interpretation of the data derived from the animal models.

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Renal Effects of Coxsackie B4 Virus in Hyper-IgA Mice

Cited by 14 publications

References 18 publications

Toll-Like Receptor 9 Affects Severity of IgA Nephropathy

Toll-Like Receptor 9 Affects Severity of IgA Nephropathy

Role of Vascular Endothelial Growth Factor and Angiopoietin 1 in Renal Injury in Hemolytic Uremic Syndrome

Prospects and Perspectives on IgA Nephropathy from Animal Models

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