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Published on: August 19, 2020
SPARC accelerates disease progression in experimental crescentic glomerulonephritis.
Amy N Sussman1, Tong Sun, Ronald M Krofft
1Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, Washington 98195, USA. amyns@u.washington.edu
The American Journal of Pathology
|April 4, 2009
Summary
Secreted protein acidic and rich in cysteine (SPARC) promotes podocyte loss in kidney disease. Removing SPARC protects against glomerulosclerosis and reduces proteinuria in experimental models.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Podocytopenia is a key feature of glomerular diseases, often preceding glomerulosclerosis.
- Podocyte detachment contributes to podocyte loss, but the mechanisms are not fully understood.
- Secreted protein acidic and rich in cysteine (SPARC) increases with podocyte injury and has counteradhesive properties.
Purpose of the Study:
- To investigate the role of SPARC in mediating experimental crescentic glomerulonephritis.
- To determine if SPARC contributes to podocyte detachment and glomerulosclerosis progression.
Main Methods:
- Induction of passive nephrotoxic nephritis in SPARC(+/+) and SPARC(-/-) mice.
- Assessment of podocyte number, glomerulosclerosis, and proteinuria at multiple time points.
- In vitro podocyte detachment assays under mechanical strain and trypsin digestion.
Main Results:
- SPARC(-/-) mice exhibited preserved podocyte numbers, reduced glomerulosclerosis, and lower proteinuria compared to SPARC(+/+) littermates.
- Reduced urinary nephrin and podocin levels correlated with preserved podocyte counts in SPARC(-/-) mice.
- SPARC-deficient podocytes showed increased resistance to stretch-induced detachment in vitro.
Conclusions:
- SPARC plays a causal role in mediating podocyte detachment.
- SPARC exacerbates glomerulosclerosis in experimental crescentic glomerulonephritis.
- Targeting SPARC may offer a therapeutic strategy for glomerular diseases.
