Investigate the Effect of Estrogen in IgA Nephropathy with in Vivo and in Vitro Model

探討性荷爾蒙再IgA腎炎纖維化角色之研究

林裕峰(Y. F. Lin) ； 莊千慧(C. H. Chuang) ； 陳金順(G. S. Chen) ； 陳安(A. Chen)

《Acta Nephrologica》 14卷4期 (2000/10) Pp. 337-337

並列摘要

IgA nephropathy (IgAN) is the most common glomeruolnephritis in Taiwan, leading to progressive renal failure in almost one third of the cases. It is characterized by deposition of IgA immune complexes (IgAIC) in the glomerular mesangium. Mesangial cells in vitro are known to bind IgA and this can trigger a number of events, principally enchanced proliferation, cytokine release, and extracellular matrix production. Currently, mesangial cells have been demonstrated to express functional IgA receptors. Even though, the mechanisms of IgA immune complexes eposition ans the consequent initiation of glomerular injury remain unknown. The objective of this study is to determine the effects of IgA immune complexes on mesangia cell by cDNA microarray analysis.
We designed the in vivo and in vitro models for disease investigation. The mouse cell line CRL1927, which purchased from American Type Culture collection (ATCC), was stimulated with IgAIC, which are composed of TEPC-15 ascites (ogA anti-phosphorylcholine) and pneumococcal c-polysaccharide, purified from streptococcus pneumonia, R36 strain. Subsequently, gene expression profile was survey with cDNA microarray. IgAN mice model also was induced by injection of IgAIC. Finally, these two models all received estradiol therapy, then fibronectin level and pathological pattern were evaluated.
From in vitro data, IgAIC-induced mesangial cell line model showed significantly more severe proliferation since day5, then reached a peak on day9. The cells, on day9, were harvested to receive cDNA microarray (6000spots) analysis. We found that hundrends of overexpressed and underexpressed genes, which will severe as candidate for pathogenesis investigation. Fibronectin, one of overexpressed genes, was selected to study, because it was related to cell growth and proliferation. Hence, we measured fibronection level in IgAIC-induced mesangial cell model and animal model, respectively. In cell model, respectively. In cell model, the level of fibronectin was significantly increased in culture medium when compared with control group (127.6±2.68 μg/ml; p＜0.05). both models receive sex hormone therapy (17ß estradiol and Tamoxifen), they all became more severe than no treatment disease model in fibronectin level. (cell model:212±62 μg/ml vs 116.2 ± 1.2 μg/ml and 16 8± 44.1 μg/ml, P＜0.05; animal model: 2.23±0.07 mg/m vs 1.85±0.08 mg/ml and 2.44±0.07 mg/ml vs 1.85±0.08 mg/ml, p＜0.05). in animal model after sex hormone therapy, we also found deterioration of pathological pattern and downhill renal function when compared with no treatment disease model. (blood urea nitrogen:51.69±2.23 mg/dl vs. 55.95±3.18 mg/dl; creatinine: 2.94±0.08 mg/dl vs. 3.14±0.06 mg/dl)
We suggest that 1). Sex hormone therapy has negative effect on IgA nephropathy mice model; 2). In IgA nephropathy, fibronectin may play a major role in disease progression, including mesangial cell proliferation, matrix expansion and fibrosis.