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beta-Catenin mediates adriamycin-induced albuminuria and podocyte injury in adult mouse kidneys.
Heikkilä, Eija; Juhila, Juuso; Lassila, Markus; Messing, Marcel; Perälä, Nina; Lehtonen, Eero; Lehtonen, Sanna; Sjef Verbeek, Joseph; Holthofer, Harry.
Afiliação
  • Heikkilä E; Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Finland.
Nephrol Dial Transplant ; 25(8): 2437-46, 2010 Aug.
Article em En | MEDLINE | ID: mdl-20237062
BACKGROUND: Glomerular slit diaphragm (SD) represents a modified adherens junction composed of molecules belonging to both immunoglobulin and cadherin superfamilies. Cadherins associate with the cytosolic scaffolding protein beta-catenin, but the precise role of beta-catenin in mature or injured podocytes is not known. METHODS: The conditional podocyte-specific beta-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-loxP system. Expression of the beta-catenin-deficient gene was turned off at the age of 8 weeks by doxycycline treatment and the kidney phenotype was analysed. In addition, beta-catenin-deficient and control mice were treated with adriamycin (ADR) and analysed for albuminuria and morphological alterations. RESULTS: Deletion of beta-catenin in mature podocytes did not change the morphology of podocytes nor did it lead to albuminuria. However, lack of beta-catenin attenuated albuminuria after ADR treatment. Electron microscopic examination showed increased podocyte foot process effacement associated with SD abnormalities in ADR-treated control mice compared to beta-catenin-deficient mice. CONCLUSIONS: These results show that beta-catenin in podocytes is dispensable for adult mice, but appears to be important in modulating the SD during ADR-induced perturbation of the filtration barrier.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doxorrubicina / Albuminúria / Beta Catenina / Glomérulos Renais / Antibióticos Antineoplásicos Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doxorrubicina / Albuminúria / Beta Catenina / Glomérulos Renais / Antibióticos Antineoplásicos Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article