Laboratory of Renal Physiology and Experimental Nephrology, Department of System Biology/Physiology Unit, University of Alcalá, Alcalá de Henares (28871), Spain.
J Cell Physiol. 2014 Dec;229(12):2057-66. doi: 10.1002/jcp.24665.
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-(10 nM and 100 nM, 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 (50 mg/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.
双酚 A，一种用于食品和饮料容器的塑料衬里生产的化学物质，在人体液中含量很高。最近，双酚 A 与成人和儿童的低水平白蛋白尿有关。由于肾小球上皮细胞（足细胞）在蛋白尿条件下通常受到影响，因此我们在此探讨了双酚 A 对体外和体内足细胞的影响。在培养的足细胞上，我们首先观察到双酚 A（低浓度或高浓度，分别为 10 nM 和 100 nM）能够诱导肥大、降低活力并促进细胞凋亡。我们还发现 TGF-β1 及其受体、细胞周期蛋白依赖性激酶抑制剂 p27Kip1 的蛋白表达增加，以及胶原-IV 的表达增加，同时观察到裂孔隔膜蛋白 Nephrin 和 Podocin 的表达减少。此外，用双酚 A（50mg/kg，腹腔注射，持续 5 周）处理的小鼠尿白蛋白排泄量和内源性肌酐清除率增加。肾脏组织学显示系膜扩张。在超微结构水平上，足细胞的细胞质和足突均增大，染色质浓缩，提示细胞凋亡。此外，WT-1（特异性足细胞标志物）的免疫组化和 TUNEL 技术分别显示出足细胞减少和凋亡的存在。总之，我们的数据表明，双酚 A 暴露会导致蛋白尿、肾小球高滤过和足细胞减少的足细胞病。需要进一步的研究来阐明双酚 A 在肾脏疾病发病机制和进展中的潜在作用。
