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Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2003 May; Vol. 14 (5), pp. 1154-63. - Publication Year :
- 2003
-
Abstract
- Dynamic recovery of glomerular structure occurs after severe glomerular damage in anti-Thy-1 glomerulonephritis (Thy-1 GN), but its mechanism remains to be investigated. To identify candidate genes possibly involved in glomerular reconstruction, screening was performed for genes that are specifically expressed by podocytes and are upregulated in glomeruli of Thy-1 GN. Among them, cysteine-rich protein 61 (Cyr61 or CCN1), a soluble angiogenic protein belonging to the CCN family, was identified. By Northern blot analysis, Cyr61 mRNA was markedly upregulated in glomeruli of Thy-1 GN from day 3 through day 7, when mesangial cell migration was most prominent. By in situ hybridization and immunohistochemistry, Cyr61 mRNA and protein were expressed by proximal straight tubules and afferent and efferent arterioles in normal rat kidneys and were intensely upregulated at podocytes in Thy-1 GN. Platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta1 (TGF-beta1), of which the gene expression in the glomeruli of Thy-1 GN was upregulated in similar time course as Cyr61, induced Cyr61 mRNA expression in cultured podocytes. Furthermore, supernatant of Cyr61-overexpressing cells inhibited PDGF-induced mesangial cell migration. In conclusion, it is shown that Cyr61 is strongly upregulated at podocytes in Thy-1 GN possibly by PDGF and TGF-beta. Cyr61 may be involved in glomerular remodeling as a factor secreted from podocytes to inhibit mesangial cell migration.
- Subjects :
- Angiogenesis Inducing Agents pharmacology
Animals
Antibodies, Monoclonal pharmacology
Becaplermin
Cell Division physiology
Cell Line, Transformed
Cell Movement physiology
Cysteine-Rich Protein 61
Disease Models, Animal
Gene Expression drug effects
Gene Expression physiology
Gene Library
Glomerulonephritis pathology
Mice
Platelet-Derived Growth Factor pharmacology
Proto-Oncogene Proteins c-sis
Rats
Thy-1 Antigens immunology
Transforming Growth Factor beta pharmacology
Transforming Growth Factor beta1
Up-Regulation
Glomerular Mesangium cytology
Glomerulonephritis physiopathology
Immediate-Early Proteins genetics
Intercellular Signaling Peptides and Proteins genetics
Neovascularization, Physiologic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1046-6673
- Volume :
- 14
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 12707386
- Full Text :
- https://doi.org/10.1097/01.asn.0000060576.61218.3d