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08:06
Guided Differentiation of Mature Kidney Podocytes from Human Induced Pluripotent Stem Cells Under Chemically Defined Conditions
Published on: July 2, 2020
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Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function
J A Hurcombe1, P Hartley2, A C Lay1
1Bristol Renal, Dorothy Hodgkin Building, University of Bristol, Bristol, BS1 3NY, UK.
Nature Communications
|January 26, 2019
Summary
Glycogen Synthase Kinase 3 (GSK3) is crucial for kidney podocyte function. Inhibiting GSK3 in mice and Drosophila leads to kidney failure and cell death, highlighting its importance in preventing albuminuria.
Area of Science:
- Nephrology
- Cell Biology
- Developmental Biology
Background:
- Albuminuria is a major risk factor for kidney failure and cardiovascular disease.
- Glomerular podocytes are essential for preventing albuminuria.
Purpose of the Study:
- To investigate the evolutionary importance of Glycogen Synthase Kinase 3 (GSK3) in maintaining podocyte function.
- To elucidate the mechanism by which GSK3 regulates podocyte integrity.
Main Methods:
- Developmental deletion of GSK3 isoforms (α and β) in murine podocytes.
- GSK3 silencing in Drosophila nephrocytes.
- Genetic and pharmacological inhibition of GSK3 in mature podocytes/nephrocytes.
Main Results:
- Developmental deletion of GSK3 caused neonatal death with massive albuminuria and renal failure in mice.
- GSK3 inhibition in mature podocytes/nephrocytes led to albuminuric kidney disease and cell depletion.
- GSK3 loss induced podocyte cell cycle re-entry and mitotic catastrophe via the Hippo pathway.
Conclusions:
- GSK3 is essential for the terminal differentiation and maintenance of kidney podocytes.
- GSK3 plays a conserved, critical role in preventing kidney disease across species.
- Targeting GSK3 may offer therapeutic avenues for albuminuric kidney diseases.
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