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ABSTRACT: The SA gene has been shown to be much more highly expressed in the kidneys of spontaneously hypertensive rats than in the corresponding wild-type strain. Genetic polymorphism of this gene has been shown to play a role in human hypertension, although the details of this association remain controversial. We investigated the possible associations between SA gene polymorphism and both hypertension and the prognosis of renal function in patients with immunoglobulin A nephropathy (IgAN). Genomic DNA was isolated from the peripheral blood of 367 individuals, including 274 patients with histologically proven IgAN and 100 controls without any history of renal disease. The SA genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) with Pst I. The frequencies of genotypes and alleles were not different between the patients with IgAN and those without renal disease. In the group without renal disease, the SA gene polymorphism was not associated with hypertension. However, in the patients with IgAN the A1 allele frequency was significantly higher in the hypertensives than in the normotensives. The renal survival of the patients with the A2 allele tended to be better than that of those without the A2 allele. The findings thus suggest that SA gene polymorphism may be associated with the renal prognosis of IgAN through its effect on blood pressure. Further, they suggest that the sensitivity to this gene polymorphism increases in patients with renal injury.
Hypertension Research 12/2002; 25(6):831-6. · 2.58 Impact Factor
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Yumi Ito,
Hiroshi Kawachi, Yoshio Morioka,
Takeshi Nakatsue,
Hiroko Koike,
Yohei Ikezumi,
Akihisa Oyanagi,
Yasuhiro Natori,
Yumiko Natori,
Takamichi Nakamura,
Fumitake Gejyo,
Fujio Shimizu
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ABSTRACT: We established the reversible and the prolonged models of mesangial proliferative glomerulonephritis (GN) with anti-Thy 1 antibody 1-22-3. However, the essential factors leading to the prolonged glomerular alterations have not been identified.
The expressions of several chemokines and cytokines were compared in the reversible and the prolonged models. Expression of fractalkine and the number of the fractalkine receptor CX3CR1-positive cells in the glomeruli in the prolonged model were significantly higher than those in the reversible model. Then, the localization of fractalkine and the characteristics of CX3CR1+ cells were analyzed in glomeruli. To elucidate the significance of the fractalkine expression, we analyzed the expression in the model treated with angiotensin II receptor antagonist, candesartan.
Immunostaining of fractalkine was detected on endothelial cells on the fifth day, and fractalkine staining also was detected in the mesangial area on day 14. Major parts of the CX3CR1+ cells in the glomeruli were macrophages, especially ED3+ cells. Candesartan treatment ameliorated the glomerular morphological findings at six weeks after disease induction. Although the treatment did not ameliorate the morphological finding at two weeks, decreased expression of fractalkine and CX3CR1+ were already detected at two weeks in rats treated with candesartan.
Fractalkine expression and the recruitment of CX3CR1+ cells in glomeruli might play an important role in the development of the prolonged disease. These expressions could be predictors of the prolonged disease of the mesangial proliferative glomerulonephritis.
Kidney International 07/2002; 61(6):2044-57. · 6.61 Impact Factor
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Yumi Ito,
Hiroshi Kawachi, Yoshio Morioka,
Takeshi Nakatsue,
Hiroko Koike,
Yohei Ikezumi,
Akihisa Oyanagi,
Yasuhiro Natori,
Yumiko Natori,
Takamichi Nakamura,
Fumitake Gejyo,
Fujio Shimizu
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ABSTRACT: Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis.Background We established the reversible and the prolonged models of mesangial proliferative glomerulonephritis (GN) with anti-Thy 1 antibody 1-22-3. However, the essential factors leading to the prolonged glomerular alterations have not been identified.
Kidney International 05/2002; 61(6):2044-2057. · 6.61 Impact Factor
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ABSTRACT: We compared the acute phase responses of mesangial cells and inflammatory cells in reversible and irreversible mesangial alterations. We used a reversible model that induced by a single injection of anti-Thy 1.1 monoclonal antibody (mAb) 1-22-3,and an irreversible model of glomerulonephritis induced by two consecutive injections of mAb 1-22-3 with an interval of 2 weeks. Similar mesangiolysis occurred in both models. However, pathological phenotypic changes in the mesangial cell began more rapidly and markedly after the second wave of mesangiolysis. Glomerular mRNA expression of platelet-derived growth factor (PDGF) was higher in the irreversible model than in the reversible model, whereas mRNA expression of monocyte chemoattractant protein-1 (MCP-1) was lower in the irreversible model. The numbers of polymorphonuclear cell (PMN) and ED1^+ monocytes/macrophages were lower in the irreversible model than in the reversible model. By contrast, the recruitment of ED3^+ cells into the glomeruli was dominant in the irreversible model. A dual labeling study showed that major parts of ED3^+ cells in the glomeruli of the irreversible model were ED1 negative. ED3^+ ED1^- cells were not detected at any time in the reversible model. The ED3^+ cell should be regarded as an important candidate for acting on the mesangial cell to lead to irreversible mesangial alterations.
