Background: IgA nephropathy (IgAN) is characterized by the deposition of the IgA1-IgG immune complex in glomerular mesangial areas. The progression of IgAN in patients is more prominent in men than women. Grouped ddY (gddY) mice are a useful animal model for IgAN patients. However, the mechanisms underlying the gender difference in IgAN has not been clearly understood. Method:We divided female gddY mice into 4 groups as follows: 4 weeks and 14 weeks control mice (4wFC, 14wFC), 14 week-old ovariectomy mice (14wOvx), and 17β-Estrodiol (E2) replaced ovariectomy mice (14wO + E2). Levels of the urinary albumin creatinine ratio (ACR), serum IgA and IgA-IgG Immune complex (IC) concentrations, and renal histopathological findings were examined. In order to elucidate the renal protective effects of E2, we examined estrogen receptors (Erα, Erβ), TGF-β1 mRNA expressions, and the number of F4/80 positive macrophages. Results:The numbers of sclerotic glomeruli were increased in 14wFC compared with 4wFC. The numbers of advanced sclerotic glomeruli in 14wOvx were reduced by half in 14wO + E2. Urinary ACR and serum IgA and IgA-IgG concentration were increased in 14wOvx and recovered by E2 replacement. Similar changes were observed in the intensity of IgA, IgG, and C3 depositions in glomeruli by immunofluorescence. The numbers of F4/80 positive cells were increased in 14wOvx and recovered to the levels of 14wFC in 14wO + E2. Erα mRNA was increased in 14wOvx but Erβ mRNA was increased in 14wO + E2 compared with 14wFC, suggesting exogenous E2 affects through Erα. TGF-β1 mRNA was increased in 14wOvx and recovered to the 14wFC level by E2 replacement. Conclusion: Estrogen deficiency accelerates the progression of glomerular injury suggesting a contribution to the gender difference in IgAN. Macrophage infiltration, estrogen receptors (Erα, Erβ), and TGF-β1 metabolism may be involved in the progression of IgAN.
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