Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2010
beta-Catenin mediates adriamycin-induced albuminuria and podocyte injury in adult mouse kidneys.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Heikkilä Eija, Juhila Juuso, Lassila Markus, Messing Marcel, Perälä Nina, Lehtonen Eero, Lehtonen Sanna, Sjef Verbeek Joseph, Holthofer Harry
Аннотация
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.
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.