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Podocyte GSK3α is important for autophagy and its loss detrimental for glomerular function

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)498-510
Number of pages13
JournalFASEB BioAdvances
Volume1
Issue number8
Early online date1 Jul 2019
DOIs
DateAccepted/In press - 20 Jun 2019
DateE-pub ahead of print - 1 Jul 2019
DatePublished (current) - 5 Aug 2019

Abstract

Podocytes are key cells in maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Glycogen synthase kinase 3 (GSK3) is a multi-functional serine/threonine kinase existing as two distinct but related isoforms (α and β). In the podocyte it has previously been reported that inhibition of the β isoform is beneficial in attenuating a variety of glomerular disease models but loss of both isoforms is catastrophic. However, it is not known what the role of GSK3α is in these cells. We now show that GSK3α is present and dynamically modulated in podocytes. When GSK3α is transgenically knocked down specifically in the podocytes of mice it causes mild but significant albuminuria by 6-weeks of life. Its loss also does not protect in models of diabetic or Adriamycin-induced nephropathy. In vitro deletion of podocyte GSK3α causes cell death and impaired autophagic flux suggesting it is important for this key cellular process. Collectively this work shows that GSK3α is important for podocyte health and that augmenting its function may be beneficial in treating glomerular disease.

    Research areas

  • Diabetic nephropathy, insulin signaling, Adriamycin nephropathy, albuminuria

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Wiley at https://onlinelibrary.wiley.com/doi/full/10.1096/fba.2019-00011. Please refer to any applicable terms of use of the publisher.

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