β-Catenin mediates adriamycin-induced albuminuria and podocyte injury in adult mouse kidneys
E Heikkilä, J Juhila, M Lassila… - Nephrology Dialysis …, 2010 - academic.oup.com
E Heikkilä, J Juhila, M Lassila, M Messing, N Perälä, E Lehtonen, S Lehtonen…
Nephrology Dialysis Transplantation, 2010•academic.oup.comBackground. 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 β-catenin, but the precise role of β-
catenin in mature or injured podocytes is not known. Methods. The conditional podocyte-
specific β-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-
loxP system. Expression of the β-catenin-deficient gene was turned off at the age of 8 weeks …
composed of molecules belonging to both immunoglobulin and cadherin superfamilies.
Cadherins associate with the cytosolic scaffolding protein β-catenin, but the precise role of β-
catenin in mature or injured podocytes is not known. Methods. The conditional podocyte-
specific β-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-
loxP system. Expression of the β-catenin-deficient gene was turned off at the age of 8 weeks …
Abstract
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 β-catenin, but the precise role of β-catenin in mature or injured podocytes is not known.
Methods. The conditional podocyte-specific β-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-loxP system. Expression of the β-catenin-deficient gene was turned off at the age of 8 weeks by doxycycline treatment and the kidney phenotype was analysed. In addition, β-catenin-deficient and control mice were treated with adriamycin (ADR) and analysed for albuminuria and morphological alterations.
Results. Deletion of β-catenin in mature podocytes did not change the morphology of podocytes nor did it lead to albuminuria. However, lack of β-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 β-catenin-deficient mice.
Conclusions. These results show that β-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.
Oxford University Press