SPARC is expressed by mesangial cells in experimental mesangial proliferative nephritis and inhibits platelet-derived-growth-factor-mediated mesangial cell proliferation in vitro

Raimund H. Pichler*, James A. Bassuk, Christian Hugo, May J. Reed, Eudora Eng, Katherine L. Gordon, Jeffrey Pippin, Charles E. Alpers, William G. Couser, E. Helene Sage, Richard J. Johnson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Mesangial cell proliferation is a characteristic feature of many glomerular diseases and often precedes extracellular matrix expansion and glomerulosclerosis. This study provides the first evidence that SPARC (secreted protein acidic and rich in cysteine) could be an endogenous factor mediating resolution of experimental mesangial proliferative nephritis in the rat. SPARC is a platelet-derived-growth-factor-binding glycoprotein that inhibits proliferation of endothelial cells and fibroblasts. We now show that SPARC is synthesized by mesangial cells in culture and that SPARC mRNA levels are increased by platelet-derived growth factor and basic fibroblast growth factor. Recombinant SPARC or the synthetic SPARC peptide 2.1 inhibited platelet-derived-growth-factor-induced mesangial cell DNA synthesis in vitro. In a model of experimental mesangioproliferative glomerulonephritis, SPARC mRNA was increased 5-fold by day 7 and was identified in the mesangium by in situ hybridization. Similarly, SPARC was increased in glomerular mesangial cells and visceral epithelial cells by day 5 and reached maximal expression levels by day 7 Mesangial cell proliferation increased by 36-fold on day 5 and decreased abruptly on day 7. Maximal expression of SPARC was correlated with the resolution of mesangial cell proliferation. We propose that SPARC functions in part as an endogenous inhibitor of platelet-derived-growth- factor-mediated mesangial cell proliferation in glomerulonephritis and that it could account for the resolution of cellular proliferation in this disease.

Original languageEnglish (US)
Pages (from-to)1153-1167
Number of pages15
JournalAmerican Journal of Pathology
Volume148
Issue number4
StatePublished - Apr 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'SPARC is expressed by mesangial cells in experimental mesangial proliferative nephritis and inhibits platelet-derived-growth-factor-mediated mesangial cell proliferation in vitro'. Together they form a unique fingerprint.

Cite this