Abstract
Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells in culture, is expressed in vivo in a variety of inflammatory conditions associated with cell proliferation, including atherosclerosis, wound repair, pulmonary fibrosis, and glomerulonephritis. However, it is not known if PDGF mediates the fibroproliferative responses that characterize these inflammatory disorders. We administered neutralizing anti-PDGF IgG or control IgG to rats with mesangial proliferative nephritis. Inhibition of PDGF resulted in a significant reduction in mesangial cell proliferation, and largely prevented the increased deposition of extracellular matrix associated with the disease. This suggests that PDGF may have a central role in proliferative glomerular disease.
Full Text
The Full Text of this article is available as a PDF (680.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Border W. A., Okuda S., Languino L. R., Ruoslahti E. Transforming growth factor-beta regulates production of proteoglycans by mesangial cells. Kidney Int. 1990 Feb;37(2):689–695. doi: 10.1038/ki.1990.35. [DOI] [PubMed] [Google Scholar]
- Border W. A., Okuda S., Languino L. R., Sporn M. B., Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature. 1990 Jul 26;346(6282):371–374. doi: 10.1038/346371a0. [DOI] [PubMed] [Google Scholar]
- Ferns G. A., Raines E. W., Sprugel K. H., Motani A. S., Reidy M. A., Ross R. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science. 1991 Sep 6;253(5024):1129–1132. doi: 10.1126/science.1653454. [DOI] [PubMed] [Google Scholar]
- Floege J., Burns M. W., Alpers C. E., Yoshimura A., Pritzl P., Gordon K., Seifert R. A., Bowen-Pope D. F., Couser W. G., Johnson R. J. Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model. Kidney Int. 1992 Feb;41(2):297–309. doi: 10.1038/ki.1992.42. [DOI] [PubMed] [Google Scholar]
- Floege J., Johnson R. J., Gordon K., Iida H., Pritzl P., Yoshimura A., Campbell C., Alpers C. E., Couser W. G. Increased synthesis of extracellular matrix in mesangial proliferative nephritis. Kidney Int. 1991 Sep;40(3):477–488. doi: 10.1038/ki.1991.235. [DOI] [PubMed] [Google Scholar]
- Gesualdo L., Pinzani M., Floriano J. J., Hassan M. O., Nagy N. U., Schena F. P., Emancipator S. N., Abboud H. E. Platelet-derived growth factor expression in mesangial proliferative glomerulonephritis. Lab Invest. 1991 Aug;65(2):160–167. [PubMed] [Google Scholar]
- Iida H., Seifert R., Alpers C. E., Gronwald R. G., Phillips P. E., Pritzl P., Gordon K., Gown A. M., Ross R., Bowen-Pope D. F. Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6560–6564. doi: 10.1073/pnas.88.15.6560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson R. J., Garcia R. L., Pritzl P., Alpers C. E. Platelets mediate glomerular cell proliferation in immune complex nephritis induced by anti-mesangial cell antibodies in the rat. Am J Pathol. 1990 Feb;136(2):369–374. [PMC free article] [PubMed] [Google Scholar]
- Johnson R. J., Pritzl P., Iida H., Alpers C. E. Platelet-complement interactions in mesangial proliferative nephritis in the rat. Am J Pathol. 1991 Feb;138(2):313–321. [PMC free article] [PubMed] [Google Scholar]
- MacKay K., Striker L. J., Stauffer J. W., Doi T., Agodoa L. Y., Striker G. E. Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells. J Clin Invest. 1989 Apr;83(4):1160–1167. doi: 10.1172/JCI113996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shultz P. J., DiCorleto P. E., Silver B. J., Abboud H. E. Mesangial cells express PDGF mRNAs and proliferate in response to PDGF. Am J Physiol. 1988 Oct;255(4 Pt 2):F674–F684. doi: 10.1152/ajprenal.1988.255.4.F674. [DOI] [PubMed] [Google Scholar]
- Silver B. J., Jaffer F. E., Abboud H. E. Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1056–1060. doi: 10.1073/pnas.86.3.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshimura A., Gordon K., Alpers C. E., Floege J., Pritzl P., Ross R., Couser W. G., Bowen-Pope D. F., Johnson R. J. Demonstration of PDGF B-chain mRNA in glomeruli in mesangial proliferative nephritis by in situ hybridization. Kidney Int. 1991 Sep;40(3):470–476. doi: 10.1038/ki.1991.234. [DOI] [PubMed] [Google Scholar]