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An Efficient Sieving Method to Isolate Intact Glomeruli from Adult Rat Kidney
Published on: November 1, 2018
WT1-dependent sulfatase expression maintains the normal glomerular filtration barrier
Valérie A Schumacher1, Ursula Schlötzer-Schrehardt, S Ananth Karumanchi
1Department of Medicine, Children’s Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA. Valerie.Schumacher@childrens.harvard.edu
Journal of the American Society of Nephrology : JASN
|July 2, 2011
Summary
Wilms' Tumor 1 (WT1) controls kidney filtration by regulating heparan sulfate proteoglycans. Loss of Sulf1 and Sulf2 enzymes, regulated by WT1, causes kidney dysfunction and proteinuria in mice.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Podocyte-endothelial cell paracrine signaling via vascular endothelial growth factor A (VEGFA) is crucial for glomerular filtration.
- Heparan sulfate proteoglycans (HSPGs) influence VEGFA bioavailability, but their role in podocyte-endothelial cell crosstalk is unclear.
Purpose of the Study:
- To investigate the role of Wilms' Tumor 1 (WT1) in modulating HSPGs and their impact on glomerular filtration.
Main Methods:
- Investigated WT1's regulation of 6-O-endosulfatases (Sulf1 and Sulf2) involved in heparan sulfate remodeling.
- Generated and analyzed mice deficient in both Sulf1 and Sulf2.
- Examined kidney structure, proteinuria, and growth factor distribution in these mice.
Main Results:
- WT1 upregulates Sulf1 and Sulf2, which modify heparan sulfate patterns.
- Sulf1/Sulf2 deficiency in mice leads to age-dependent proteinuria and kidney defects.
- These defects resemble those in WT1-mutated individuals and Wt1(+/-) mice, with reduced VEGFA distribution.
Conclusions:
- WT1-dependent sulfatase expression is critical for maintaining the glomerular filtration barrier.
- Modulation of growth factor bioavailability by WT1-regulated sulfatases ensures proper podocyte-endothelial cell communication.
- This pathway is essential for preventing kidney dysfunction and proteinuria.
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