beta-Catenin mediates adriamycin-induced albuminuria and podocyte injury in adult mouse kidneys.
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.
Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Finland.
Eija
E
Heikkilä
Juuso
J
Juhila
Markus
M
Lassila
Marcel
M
Messing
Nina
N
Perälä
Eero
E
Lehtonen
Sanna
S
Lehtonen
Joseph
J
Sjef Verbeek
Harry
H
Holthofer
D000419:Albuminuria / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D051176:beta Catenin; C113267:nephrin; D004317:Doxorubicin