title: Bisphenol-A induces podocytopathy with proteinuria in mice.
abstract: 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.
authors.affiliation: Laboratory of Renal Physiology and Experimental Nephrology, Department of System Biology/Physiology Unit, University of Alcalá, Alcalá de Henares (28871), Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Olea-Herrero
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Arenas
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñóz-Moreno
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Gómez-Toledano
authors.forename: Marta
authors.initials: M
authors.lastname: González-Santander
authors.forename: Ignacio
authors.initials: I
authors.lastname: Arribas
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Bosch
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds