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首页> 外文期刊>Journal of Cellular Physiology >Bisphenol-A induces podocytopathy with proteinuria in mice
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Bisphenol-A induces podocytopathy with proteinuria in mice

机译:双酚a诱发podocytopathy蛋白尿在老鼠身上

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Bisphenol-A, a chemical used in the production of the plastic lining of food and beverage containers, can be found in significant levels in human fluids. Recently, bisphenol-A has been associated with low-grade albuminuria in adults as well as in children. Since glomerular epithelial cells (podocytes) are commonly affected in proteinuric conditions, herein we explored the effects of bisphenol-A on podocytes in vitro and in vivo. On cultured podocytes we first observed that bisphenol-A-at low or high concentrations-(10nM and 100nM, respectively) was able to induce hypertrophy, diminish viability, and promote apoptosis. We also found an increase in the protein expression of TGF-β1 and its receptor, the cyclin-dependent kinase inhibitor p27Kip1, as well as collagen-IV, while observing a diminished expression of the slit diaphragm proteins nephrin and podocin. Furthermore, mice intraperitoneally injected with bisphenol-A (50mg/Kg for 5 weeks) displayed an increase in urinary albumin excretion and endogenous creatinine clearance. Renal histology showed mesangial expansion. At ultrastructural level, podocytes displayed an enlargement of both cytoplasm and foot processes as well as the presence of condensed chromatin, suggesting apoptosis. Furthermore, immunohistochemistry for WT-1 (specific podocyte marker) and the TUNEL technique showed podocytopenia as well as the presence of apoptosis, respectively. In conclusion, our data demonstrate that Bisphenol-A exposure promotes a podocytopathy with proteinuria, glomerular hyperfiltration and podocytopenia. Further studies are needed to clarify the potential role of bisphenol-A in the pathogenesis as well as in the progression of renal diseases.
机译:化工生产中使用双酚a食品和饮料的塑料衬里容器,可以在显著水平人类的液体。与成人轻度蛋白尿有关以及孩子。上皮细胞(足细胞)是常见的影响proteinuric条件,在此我们研究双酚a对足细胞的影响在体外和体内。第一次观察到bisphenol-A-at低或高浓度(分别为10和100 nm)能够诱导肥大,减少生存能力,并促进细胞凋亡。蛋白表达的TGF -β1和它受体,细胞周期蛋白依赖性激酶抑制剂p27Kip1、collagen-IV,而观察减少表达式的狭缝隔膜nephrin和podocin的蛋白质。腹腔内注射双酚a(50毫克/公斤5周)显示的增加尿白蛋白排泄和内生肌酐清除率。系膜扩张。足细胞的扩大都显示细胞质和脚过程以及凝聚染色质,建议细胞凋亡。WT-1(足细胞的特定标记)和TUNEL技术显示podocytopenia以及分别存在细胞凋亡。结论:我们的数据表明,双酚a接触促进podocytopathy蛋白尿、肾小球反渗透法和podocytopenia。阐明双酚a的潜在作用发病机理的进展肾脏疾病。

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