Up-Regulated TGF-β mRNA Expression in Splenic T Cells of High IgA-Prone Mice: A Murine Model of IgA Nephropathy with Glomerulosclerosis (original) (raw)

Background/Aims: Recently, we established a high serum IgA-prone inbred (HIGA) mouse strain as a murine model of spontaneous IgA nephropathy by selective mating of high serum IgA ddY mice, and found that they showed enhanced production of glomerular extracellular matrix components with increased expression of TGF-β mRNA and protein in the kidneys. In this study, we examined the roles of lymphocytes in the development of high serum IgA in this strain. Methods: We performed flow cytometric analyses of T and B cells in splenic mononuclear cells (SMNCs) from these mice using BALB/c mice as normal controls. We also compared serum TGF-β1 concentrations and TGF-β mRNA expression levels in the B-cell-depleted (T-cell-rich) fraction of SMNCs in these mice. Results: HIGA mice showed significantly fewer CD3-positive cells compared with BALB/c mice when young, but not when aged. The CD4/CD8 ratio of HIGA mice was lower than that of BALB/c mice, but this difference was not significant. Although ...

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Heminephrectomy causes the progression of glomerulosclerosis and apoptosis in high IgA strain of ddY (HIGA) mice

Nephrology, 2001

Background: The nephron reduction in IgA nephropathy is critical for the newly established prognosis of this disease. A high immunoglobulin A inbred strain of ddY mouse (HIGA mouse) showed progressive mesangial sclerosis with elevated renal expression of transforming growth factor (TGF)‐β,1 however, the progression of the renal lesion of this mouse is relatively mild with rare association of active crescentic glomerulonephritis. However, although nephron reduction causes progressive renal injury, the modifications of glomerular lesions by nephron reduction are dependent upon the pathological background of each strain. Thus, we investigated the influence of nephron reduction by heminephrectomy on the renal lesions of the HIGA mouse.Methods: Five‐week‐old HIGA mice were heminephrectomized (Nx), and were evaluated in comparison with a sham‐operated group (S) at 40 weeks old. Measurements of renal function, blood pressure and serum levels of immunoglobulins (IgG, IgA, and IgM) were perf...

Correlation between the Severity of Clinicopathological Parameters and Whole Blood Interferon-α Production Capacity in Active Phase IgA Nephropathy Patients

Nephron, 2001

Background/Aims: Patients with IgA nephropathy (IgA-N) are thought to have immune system disorders that frequently result in high serum IgA levels and a relatively high susceptibility to upper respiratory infections. Aims: To clarify the influence of the specific immune response of IgA-N patients on the clinicopathological features of the disease, we measured the whole-blood-producing capacity of interferon-α (IFNα-PC). We then compared these findings with clinical and histopathological parameters, including tissue macrophage infiltration, during both histologically active and latent phases. Patients and Methods: Fifty-one inpatients with IgA-N and 70 healthy controls were examined. According to the histological findings, 32 patients had disease in the active phase (AP), and 19 were in the latent phase (LP). Results: In AP patients, IFNα-PC showed positive correlations to serum creatinine, blood urea nitrogen, serum β2-microglobulin (s-β2MG), urinary total protein (U-TP), and urinar...

Ultrastructural Localization of Dominantly Increased Fibronectin in the Markedly Thickened Glomerular Basement Membrane in a Selectively Mated Murine High IgA Strain (HIGA Mice)

Nephron, 1999

To clarify which matrix component(s) contributes to glomerular sclerosis with mesangial IgA deposits in a murine high serum IgA strain (HIGA) derived from ddY mice, morphological and immunopathological analyses of glomeruli were performed in comparison with original ddY and BALB/c mice as controls. Significantly increased thickness of the glomerular basement membrane (GBM), especially the lamina densa, was observed in HIGA mice. Immunofluorescent staining showed marked increases in levels of fibronectin and laminin in both the mesangium and capillary wall in aged HIGA mice. Analysis of the distribution of immunogold-labeled antibody in GBM revealed a significant increase (p < 0.0001) and specific orientation of fibronectin in the endothelial side, which suggested that mesangial fibronectin produced at high levels due to IgA deposition extended to the endothelial side of GBM and contributed to the thickening of GBM with further development to glomerulosclerosis in the HIGA mice.

Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis

Journal of the American Society of Nephrology, 2003

ABSTRACT. Dynamic recovery of glomerular structure occurs after severe glomerular damage in anti-Thy-1 glomerulonephritis (Thy-1 GN), but its mechanism remains to be investigated. To identify candidate genes possibly involved in glomerular reconstruction, screening was performed for genes that are specifically expressed by podocytes and are upregulated in glomeruli of Thy-1 GN. Among them, cysteine-rich protein 61 (Cyr61 or CCN1), a soluble angiogenic protein belonging to the CCN family, was identified. By Northern blot analysis, Cyr61 mRNA was markedly upregulated in glomeruli of Thy-1 GN from day 3 through day 7, when mesangial cell migration was most prominent. By in situ hybridization and immunohistochemistry, Cyr61 mRNA and protein were expressed by proximal straight tubules and afferent and efferent arterioles in normal rat kidneys and were intensely upregulated at podocytes in Thy-1 GN. Platelet-derived growth factor–BB (PDGF-BB) and transforming growth factor–β1 (TGF-β1), of...

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