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Localization of SPARC in developing, mature, and chronically injured human allograft kidneys
Charles E Alpers1, Kelly L Hudkins, Stephan Segerer
1Department of Pathology, University of Washington School of Medicine, Seattle Washington, USA. calp@u.washington.edu
Background:
The matricellular protein SPARC (secreted protein acidic and rich in cysteine) is expressed during development, tissue remodeling and repair. It functions as an endogenous inhibitor of cell proliferation, regulates angiogenesis, regulates cell adhesion to extracellular matrix, binds cytokines such as platelet derived growth factor and stimulates transforming growth factor-beta (TGF-beta) production. This study describes the expression of SPARC during human renal development, in normal kidneys and during renal allograft rejection.
Methods:
A total of 60 renal specimens, including normal areas from tumor nephrectomies (N = 24), fetal kidneys (N = 27) and explanted renal allografts (N = 9), were included in the study. SPARC protein was localized by immunohistochemistry using two different antibodies. On consecutive sections SPARC mRNA was detected by in situ hybridization.
Results:
In the normal adult kidney SPARC protein was expressed by visceral and parietal epithelial cells, collecting duct epithelium (CD), urothelium, smooth muscle cells of muscular arteries and focally in interstitial cells. During renal development immature glomeruli demonstrated a polarized SPARC expression in visceral epithelial cells at their surface abutting the capillary basement membranes. In the fully differentiated glomeruli the expression pattern mirrored that of the adult kidney. Furthermore, SPARC was abundantly expressed by derivatives of the ureteric bud, and smooth muscle cells of arterial walls. During chronic allograft rejection SPARC is expressed in neointimal arterial smooth muscle cells, infiltrating inflammatory cells as well as by interstitial myofibroblasts in areas of interstitial fibrosis. SPARC mRNA synthesis detected by in situ hybridization mirrored these protein expression patterns.
Conclusion:
These studies co-localize SPARC to several sites of renal injury previously shown to be sites of PDGF B-chain expression and/or activity. We speculate that SPARC could function as an accessory molecule in chronic PDGF-mediated sclerosing interstitial and vascular injury. SPARC localization to glomerular epithelial cells corresponds to similar findings in rodents, and may reflect its role in cell adhesion and /or regulation of cell shape.
Insights
Secreted protein acidic and rich in cysteine (SPARC) is present in normal kidneys, during development, and in allograft rejection. SPARC may play a role in chronic kidney injury and fibrosis.
Area of Science:
- Nephrology
- Developmental Biology
- Immunology
Background:
- SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein involved in tissue remodeling and repair.
- It regulates cell proliferation, angiogenesis, cell adhesion, and cytokine binding, and stimulates TGF-beta production.
- This study investigates SPARC expression in human kidney development, normal kidneys, and renal allograft rejection.
Purpose of the Study:
- To describe the expression patterns of SPARC during human renal development.
- To analyze SPARC expression in normal adult kidneys.
- To investigate SPARC localization in renal allograft rejection.
Main Methods:
- Utilized immunohistochemistry to localize SPARC protein in 60 renal specimens.
- Employed in situ hybridization to detect SPARC mRNA on consecutive sections.
- Specimens included normal adult kidney tissue, fetal kidneys, and explanted renal allografts.
Main Results:
- SPARC protein was found in various renal cells, including epithelial cells, collecting ducts, urothelium, and arterial smooth muscle cells in normal kidneys.
- During development, SPARC showed polarized expression in immature glomeruli and was abundant in ureteric bud derivatives.
- In chronic allograft rejection, SPARC was expressed by arterial smooth muscle cells, inflammatory cells, and interstitial myofibroblasts.
Conclusions:
- SPARC localizes to sites of renal injury associated with PDGF B-chain activity.
- SPARC may function as an accessory molecule in chronic PDGF-mediated sclerosing injury.
- SPARC's localization in glomerular epithelial cells suggests a role in cell adhesion and shape regulation.