SPARC regulates the expression of collagen type I and transforming growth factor-beta 1 in mesangial cells

The matricellular protein SPARC is expressed at high levels in cells that p articipate in tissue remodeling and is thought to regulate mesangial cell p roliferation and extracellular matrix production in the kidney glomerulus i n a rat model of glomerulonephritis (Pichler, R. H., Bassuk, J. A., Hugo, C ., Reed, RI. J., Eng, E., Gordon, K. L., Pippin, J., Alpers, C. E., Couser, W. G., Sage, E. H., and Johnson, R. J. (1997) Am. J. Pathol. 148, 1153-116 7). A potential mechanism by which SPARC controls both cell cycle and matri x production has been attributed to its regulation of a pleiotropic growth factor. In this study we used primary mesangial cell cultures from wild-typ e mice and from mice with a targeted disruption of the SPARC gene. SPARC-nu ll cells displayed diminished expression of collagen type I mRNA and protei n, relative to wild-type cells, by the criteria of immunocytochemistry, imm unoblotting, and the reverse transcription-polymerase chain reaction. The S PARC-null cells also showed significantly decreased steady-state levels of transforming growth factor-beta 1 (TGF-beta 1) mRNA and secreted TGF-beta 1 protein. Addition of recombinant SPARC to SPARC-null cells restored the ex pression of collagen type I mRNA to 70% and TGF-beta 1 mRNA to 100% of wild type levels. We conclude that SPARC regulates the expression of collagen ty pe I and TGF-beta 1 in kidney mesangial cells. Since increased mitosis and matrix deposition by mesangial cells are characteristics of glomerulopathie s, we propose that SPARC is one of the factors that maintains the balance b etween cell proliferation and matrix production in the glomerulus.