This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pichler, R. H. Articles by Johnson, R. J. Search for Related Content PubMed PubMed Citation Articles by Pichler, R. H. Articles by Johnson, R. J.

American Journal of Pathology, Vol 148, 1153-1167, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

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

RH Pichler, JA Bassuk, C Hugo, MJ Reed, E Eng, KL Gordon, J Pippin, CE Alpers, WG Couser, EH Sage and RJ Johnson
Division of Nephrology, Department of Medicine, University of Washington, Seattle 98195, USA.

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.

This article has been cited by other articles:

				A. N. Sussman, T. Sun, R. M. Krofft, and R. V. Durvasula SPARC Accelerates Disease Progression in Experimental Crescentic Glomerulonephritis Am. J. Pathol., May 1, 2009; 174(5): 1827 - 1836. [Abstract] [Full Text] [PDF]

				R. V. Durvasula and S. J. Shankland Mechanical strain increases SPARC levels in podocytes: implications for glomerulosclerosis Am J Physiol Renal Physiol, September 1, 2005; 289(3): F577 - F584. [Abstract] [Full Text] [PDF]

				K.-F. Beck, G. Guder, L. Schaefer, M. Pleskova, A. Babelova, M. H. Behrens, D. Mihalik, M. Beck, R. M. Schaefer, and J. Pfeilschifter Nitric Oxide Upregulates Induction of PDGF Receptor-{alpha} Expression in Rat Renal Mesangial Cells and in Anti-Thy-1 Glomerulonephritis J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1948 - 1957. [Abstract] [Full Text] [PDF]

				B. F. Schrijvers, A. S. De Vriese, and A. Flyvbjerg From Hyperglycemia to Diabetic Kidney Disease: The Role of Metabolic, Hemodynamic, Intracellular Factors and Growth Factors/Cytokines Endocr. Rev., December 1, 2004; 25(6): 971 - 1010. [Abstract] [Full Text] [PDF]

				D. M. Sadlier, S. B. Connolly, N. E. Kieran, S. Roxburgh, D. P. Brazil, L. Kairaitis, Y. Wang, D. C. H. Harris, P. Doran, and H. R. Brady Sequential Extracellular Matrix-focused and Baited-global Cluster Analysis of Serial Transcriptomic Profiles Identifies Candidate Modulators of Renal Tubulointerstitial Fibrosis in Murine Adriamycin-induced Nephropathy J. Biol. Chem., July 9, 2004; 279(28): 29670 - 29680. [Abstract] [Full Text] [PDF]

				S. V. Vadlamuri, J. Media, S. S. Sankey, A. Nakeff, G. Divine, and S. A. Rempel SPARC affects glioma cell growth differently when grown on brain ECM proteins in vitro under standard versus reduced-serum stress conditions Neuro-oncol, October 1, 2003; 5(4): 244 - 254. [Abstract] [PDF]

				S. Taneda, J. W. Pippin, E. H. Sage, K. L. Hudkins, Y. Takeuchi, W. G. Couser, and C. E. Alpers Amelioration of Diabetic Nephropathy in SPARC-Null Mice J. Am. Soc. Nephrol., April 1, 2003; 14(4): 968 - 980. [Abstract] [Full Text] [PDF]

				D.-H. Kang, J. Kanellis, C. Hugo, L. Truong, S. Anderson, D. Kerjaschki, G. F. Schreiner, and R. J. Johnson Role of the Microvascular Endothelium in Progressive Renal Disease J. Am. Soc. Nephrol., March 1, 2002; 13(3): 806 - 816. [Abstract] [Full Text] [PDF]

				M. Yanagita, H. Arai, T. Nakano, K. Ohashi, K. Mizuno, A. Fukatsu, T. Doi, and T. Kita Gas6 Induces Mesangial Cell Proliferation via Latent Transcription Factor STAT3 J. Biol. Chem., November 2, 2001; 276(45): 42364 - 42369. [Abstract] [Full Text] [PDF]

				M. Yanagita, H. Arai, K. Ishii, T. Nakano, K. Ohashi, K. Mizuno, B. Varnum, A. Fukatsu, T. Doi, and T. Kita Gas6 Regulates Mesangial Cell Proliferation through Axl in Experimental Glomerulonephritis Am. J. Pathol., April 1, 2001; 158(4): 1423 - 1432. [Abstract] [Full Text] [PDF]

				A.-P. Gadeau, H. Chaulet, D. Daret, M. Kockx, J.-M. Daniel-Lamazière, and C. Desgranges Time Course of Osteopontin, Osteocalcin, and Osteonectin Accumulation and Calcification After Acute Vessel Wall Injury J. Histochem. Cytochem., January 1, 2001; 49(1): 79 - 86. [Abstract] [Full Text]

				S. WALPEN, K.-F. BECK, W. EBERHARDT, M. APEL, P. K. CHATTERJEE, G. M. H. WRAY, C. THIEMERMANN, and J. PFEILSCHIFTER Downregulation of SPARC Expression Is Mediated by Nitric Oxide in Rat Mesangial Cells and during Endotoxemia in J. Am. Soc. Nephrol., March 1, 2000; 11(3): 468 - 476. [Abstract] [Full Text] [PDF]

				R. Thomas, L. D. True, J. A. Bassuk, P. H. Lange, and R. L. Vessella Differential Expression of Osteonectin/SPARC during Human Prostate Cancer Progression Clin. Cancer Res., March 1, 2000; 6(3): 1140 - 1149. [Abstract] [Full Text]

				A. Francki, A. D. Bradshaw, J. A. Bassuk, C. C. Howe, W. G. Couser, and E. H. Sage SPARC Regulates the Expression of Collagen Type I and Transforming Growth Factor-beta 1 in Mesangial Cells J. Biol. Chem., November 5, 1999; 274(45): 32145 - 32152. [Abstract] [Full Text] [PDF]

				A. Mooney, K. Jackson, R. Bacon, C. Streuli, G. Edwards, J. Bassuk, and J. Savill Type IV Collagen and Laminin Regulate Glomerular Mesangial Cell Susceptibility to Apoptosis Via {beta}1 Integrin-Mediated Survival Signals Am. J. Pathol., August 1, 1999; 155(2): 599 - 606. [Abstract] [Full Text] [PDF]

				A. D. Bradshaw, A. Francki, K. Motamed, C. Howe, and E. H. Sage Primary Mesenchymal Cells Isolated from SPARC-null Mice Exhibit Altered Morphology and Rates of Proliferation Mol. Biol. Cell, May 1, 1999; 10(5): 1569 - 1579. [Abstract] [Full Text]

				A. M. Delany and E. Canalis Basic fibroblast growth factor destabilizes osteonectin mRNA in osteoblasts Am J Physiol Cell Physiol, March 1, 1998; 274(3): C734 - C740. [Abstract] [Full Text] [PDF]