Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function

Authors: Hurcombe, J., Hartley, P. and et al

http://eprints.bournemouth.ac.uk/31732/

Journal: Nature Communications

Publisher: Springer Nature

ISSN: 2041-1723

DOI: 10.1038/s41467-018-08235-1

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function

This data was imported from PubMed:

Authors: Hurcombe, J.A. et al.

http://eprints.bournemouth.ac.uk/31732/

Journal: Nat Commun

Volume: 10

Issue: 1

Pages: 403

eISSN: 2041-1723

DOI: 10.1038/s41467-018-08235-1

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.

This source preferred by Paul Hartley

This data was imported from Scopus:

Authors: Hurcombe, J.A. et al.

http://eprints.bournemouth.ac.uk/31732/

Journal: Nature Communications

Volume: 10

Issue: 1

eISSN: 2041-1723

DOI: 10.1038/s41467-018-08235-1

© 2019, The Author(s). Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.

This data was imported from Web of Science (Lite):

Authors: Hurcombe, J.A. et al.

http://eprints.bournemouth.ac.uk/31732/

Journal: NATURE COMMUNICATIONS

Volume: 10

ISSN: 2041-1723

DOI: 10.1038/s41467-018-08235-1

The data on this page was last updated at 05:30 on November 25, 2020.