Bisphenol-A Induces Podocytopathy With Proteinuria in Mice
Authors
Olea Herrero, Nuria; Arenas Jiménez, María Isabel; Muñoz Moreno, María Del Carmen; Moreno Gómez-Toledano, Rafael; González-Santander Martínez, Marta; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/50490DOI: 10.1002/jcp.24665
ISSN: 1097-4652
Date
2014Affiliation
Universidad de Alcalá. Departamento de Fisiología; Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas; Universidad de Alcalá. Departamento de Biología de SistemasFunders
Ministerio de Ciencia e Innovación
Instituto de Salud Carlos III
The Eugenio Rodríguez Pascual Foundation
Bibliographic citation
Olea-Herrero, N. et al., 2014. Bisphenol-A Induces Podocytopathy With Proteinuria in Mice. Journal of cellular physiology, 229(12), pp.2057-2066.
Project
info:eu-repo/grantAgreement/MICINN//SAF2009-12009-C02-01/ES/Estudio Coordinado De Nuevas Moleculas Implicadas En La Diabetes Mellitus: Papel De La Citokina Tweak Y Del Bisfenol A En La Nefropatia Diabetica/
PI12/02825 (Instituto de Salud Carlos III)
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
© 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
Access rights
info:eu-repo/semantics/openAccess
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-?1 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.
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bisphenol_olea_JCP_2014.pdf | 2.246Mb |
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bisphenol_olea_JCP_2014.pdf | 2.246Mb |
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