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

Jenny Hurcombe, Abigail Lay, Lan Ni, Fern Barrington, J R Woodgett, Susan E Quaggin, Gavin Welsh, Richard Coward

Research output: Contribution to journalArticle (Academic Journal)

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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.

Original languageEnglish
Pages (from-to)498-510
Number of pages13
JournalFASEB BioAdvances
Volume1
Issue number8
Early online date1 Jul 2019
DOIs
Publication statusPublished - Aug 2019

Keywords

  • Diabetic nephropathy
  • insulin signaling
  • Adriamycin nephropathy
  • albuminuria

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