SPARC Regulates the Expression of Collagen Type I and Transforming Growth Factor-β1 in Mesangial Cells*

The matricellular protein SPARC is expressed at high levels in cells that participate in tissue remodeling and is thought to regulate mesangial cell proliferation and extracellular matrix production in the kidney glomerulus in a rat model of glomerulonephritis (Pichler, R. H., Bassuk, J. A., Hugo, C., Reed, M. 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, 1153–1167). A potential mechanism by which SPARC controls both cell cycle and matrix production has been attributed to its regulation of a pleiotropic growth factor. In this study we used primary mesangial cell cultures from wild-type mice and from mice with a targeted disruption of the SPARCgene. SPARC-null cells displayed diminished expression of collagen type I mRNA and protein, relative to wild-type cells, by the criteria of immunocytochemistry, immunoblotting, and the reverse transcription-polymerase chain reaction. The SPARC-null cells also showed significantly decreased steady-state levels of transforming growth factor-β1 (TGF-β1) mRNA and secreted TGF-β1 protein. Addition of recombinant SPARC to SPARC-null cells restored the expression of collagen type I mRNA to 70% and TGF-β1 mRNA to 100% of wild-type levels. We conclude that SPARC regulates the expression of collagen type I and TGF-β1 in kidney mesangial cells. Since increased mitosis and matrix deposition by mesangial cells are characteristics of glomerulopathies, we propose that SPARC is one of the factors that maintains the balance between cell proliferation and matrix production in the glomerulus.

[1]  E. Sage,et al.  Cell cycle‐dependent nuclear location of the matricellular protein SPARC: Association with the nuclear matrix , 1999, Journal of cellular biochemistry.

[2]  E. Sage,et al.  Primary mesenchymal cells isolated from SPARC-null mice exhibit altered morphology and rates of proliferation. , 1999, Molecular biology of the cell.

[3]  E. Sage,et al.  SPARC deficiency leads to early-onset cataractogenesis. , 1998, Investigative ophthalmology & visual science.

[4]  E. Sage,et al.  SPARC (BM-40, Osteonectin) Inhibits the Mitogenic Effect of Vascular Endothelial Growth Factor on Microvascular Endothelial Cells* , 1998, The Journal of Biological Chemistry.

[5]  G. Striker,et al.  Glomerular endothelial cells synthesize collagens but little gelatinase A and B. , 1998, Journal of the American Society of Nephrology : JASN.

[6]  David W. Johnson,et al.  Renal expression of transforming growth factor-β inducible gene-h3 (βig-h3) in normal and diabetic rats1 , 1998 .

[7]  E. Sage,et al.  SPARC inhibits endothelial cell adhesion but not proliferation through a tyrosine phosphorylation‐dependent pathway , 1998, Journal of cellular biochemistry.

[8]  R. Hynes,et al.  Thrombospondin-1 Is a Major Activator of TGF-β1 In Vivo , 1998, Cell.

[9]  B. Nordlinger,et al.  Overexpression of stromelysin-3, BM-40/SPARC, and MET genes in human esophageal carcinoma: implications for prognosis. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[10]  R. Timpl,et al.  Crystal structure and mapping by site‐directed mutagenesis of the collagen‐binding epitope of an activated form of BM‐40/SPARC/osteonectin , 1998, The EMBO journal.

[11]  U. Shankavaram,et al.  Regulation of human monocyte matrix metalloproteinases by SPARC , 1997, Journal of cellular physiology.

[12]  A. Zinsmeister,et al.  Modulation of collagen gene expression by cytokines: stimulatory effect of transforming growth factor-beta1, with divergent effects of epidermal growth factor and tumor necrosis factor-alpha on collagen type I and collagen type IV. , 1997, The Journal of laboratory and clinical medicine.

[13]  M. Varedi,et al.  Cytoskeleton regulates expression of genes for transforming growth factor‐β1 and extracellular matrix proteins in dermal fibroblasts , 1997, Journal of cellular physiology.

[14]  R. Timpl,et al.  Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: characterization of the binding of vitronectin to osteonectin (BM40, SPARC). , 1997, The Biochemical journal.

[15]  D. Salant,et al.  RANTES and Monocyte Chemoattractant Protein–1 (MCP-1) Play an Important Role in the Inflammatory Phase of Crescentic Nephritis, but Only MCP-1 Is Involved in Crescent Formation and Interstitial Fibrosis , 1997, The Journal of experimental medicine.

[16]  M. Pepper,et al.  Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. , 1997, Cytokine & growth factor reviews.

[17]  W. Reutter,et al.  Transforming Growth Factor-β (TGF-β) Stimulates the Expression of β1 Integrins and Adhesion by Rat Mesangial Cells , 1996 .

[18]  R. Jaenisch,et al.  Type I collagen‐deficient Mov‐13 mice do not retain SPARC in the extracellular matrix: Implications for fibroblast function , 1996, Developmental dynamics : an official publication of the American Association of Anatomists.

[19]  K. Nagata,et al.  Intracellular interaction of collagen-specific stress protein HSP47 with newly synthesized procollagen , 1996, The Journal of cell biology.

[20]  M. Reed,et al.  SPARC is expressed by mesangial cells in experimental mesangial proliferative nephritis and inhibits platelet-derived-growth-factor-medicated mesangial cell proliferation in vitro. , 1996, The American journal of pathology.

[21]  C. Nast,et al.  Expression of transforming growth factor-β isoforms in human glomerular diseases , 1996 .

[22]  P. Bornstein,et al.  Diversity of Function Is Inherent in Matricellular Proteins: an Appraisal of Thrombospondin I , 1995 .

[23]  Y. Akai,et al.  Intraglomerular expression of transforming growth factor‐beta 1 (TGF‐β1) mRNA in patients with glomerulonephritis: quantitative analysis by competitive polymerase chain reaction , 1994, Clinical and experimental immunology.

[24]  K. Sharma,et al.  Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-beta. , 1994, The Journal of clinical investigation.

[25]  E. Sage,et al.  The biology of SPARC, a protein that modulates cell‐matrix interactions , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  M. Reed,et al.  TGF‐β1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors , 1994 .

[27]  M. Reed,et al.  Differential expression of SPARC and thrombospondin 1 in wound repair: immunolocalization and in situ hybridization. , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[28]  A. Wolthuis,et al.  Cell density modulates growth, extracellular matrix, and protein synthesis of cultured rat mesangial cells. , 1993, The American journal of pathology.

[29]  G. Engelmann.  Coordinate gene expression during neonatal rat heart development. A possible role for the myocyte in extracellular matrix biogenesis and capillary angiogenesis. , 1993, Cardiovascular research.

[30]  Z. Werb,et al.  SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway , 1993, The Journal of cell biology.

[31]  N. Sato,et al.  Platelet-derived growth factor indirectly stimulates angiogenesis in vitro. , 1993, The American journal of pathology.

[32]  C. Alpers,et al.  Visceral glomerular epithelial cells can proliferate in vivo and synthesize platelet-derived growth factor B-chain. , 1993, The American journal of pathology.

[33]  K. Resch,et al.  The inflammatory function of renal glomerular mesangial cells and their interaction with the cellular immune system , 1992, The clinical investigator.

[34]  M. Iruela-Arispe,et al.  Regulation of gene expression by SPARC during angiogenesis in vitro. Changes in fibronectin, thrombospondin-1, and plasminogen activator inhibitor-1. , 1992, The Journal of biological chemistry.

[35]  C. Alpers,et al.  Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor , 1992, The Journal of experimental medicine.

[36]  R. Ross,et al.  The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  E. Amento,et al.  Connective tissue metabolism including cytokines in scleroderma , 1991, Current opinion in rheumatology.

[38]  K. Resch,et al.  Regulation of mesangial cell proliferation. , 1991, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[39]  E. Sage,et al.  The Ca2(+)-binding glycoprotein SPARC modulates cell cycle progression in bovine aortic endothelial cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J. Wrana,et al.  Regulation of the expression of a secreted acidic protein rich in cysteine (SPARC) in human fibroblasts by transforming growth factor beta. Comparison of transcriptional and post-transcriptional control with fibronectin and type I collagen. , 1991, European journal of biochemistry.

[41]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[42]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[43]  J. Massagué.  TGF-beta signal transduction. , 1998, Annual review of biochemistry.

[44]  M. Heckmann,et al.  Transforming growth factor-beta controls cell-matrix interaction of microvascular dermal endothelial cells by downregulation of integrin expression. , 1996, The Journal of investigative dermatology.

[45]  E. Sage,et al.  Expression of biologically active human SPARC in Escherichia coli. , 1996, Archives of biochemistry and biophysics.

[46]  C. Abrass,et al.  Induction of nodular sclerosis by insulin in rat mesangial cells in vitro: studies of collagen. , 1995, Kidney international.