Abstract
We investigated whether platelet-derived growth factor (PDGF), or its receptor (PDGF-R), was upregulated in a rat model of mesangial proliferative glomerulonephritis. A marked increase in both PDGF A- and B-chain mRNA could be demonstrated in glomerular RNA by Northern blot analysis 3 and 5 days after disease induction, corresponding to the time of mesangial cell proliferation. PDGF-R beta-subunit mRNA and protein were also increased in glomeruli in mesangial proliferative nephritis, being maximal at day 5. The principal cells expressing PDGF B-chain appeared by immunostaining to be a subpopulation of mesangial cells; in contrast, the majority of the mesangial cells expressed the PDGF-R beta-subunit protein. Both complement depletion and platelet depletion significantly reduced cell proliferation and expression of both PDGF and PDGF-R. Thus, in mesangial proliferative nephritis there is a platelet- and complement-mediated induction of PDGF A and B chain and PDGF-R beta-subunit gene transcription and protein synthesis. The finding that the majority of PDGF is produced by the mesangial cell supports the role of PDGF as an autocrine growth factor in glomerulonephritis.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Betsholtz C., Johnsson A., Heldin C. H., Westermark B., Lind P., Urdea M. S., Eddy R., Shows T. B., Philpott K., Mellor A. L. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature. 1986 Apr 24;320(6064):695–699. doi: 10.1038/320695a0. [DOI] [PubMed] [Google Scholar]
- Claesson-Welsh L., Hammacher A., Westermark B., Heldin C. H., Nistér M. Identification and structural analysis of the A type receptor for platelet-derived growth factor. Similarities with the B type receptor. J Biol Chem. 1989 Jan 25;264(3):1742–1747. [PubMed] [Google Scholar]
- Doi T., Striker L. J., Elliot S. J., Conti F. G., Striker G. E. Insulinlike growth factor-1 is a progression factor for human mesangial cells. Am J Pathol. 1989 Feb;134(2):395–404. [PMC free article] [PubMed] [Google Scholar]
- Fellström B., Klareskog L., Heldin C. H., Larsson E., Rönnstrand L., Terracio L., Tufveson G., Wahlberg J., Rubin K. Platelet-derived growth factor receptors in the kidney--upregulated expression in inflammation. Kidney Int. 1989 Dec;36(6):1099–1102. doi: 10.1038/ki.1989.306. [DOI] [PubMed] [Google Scholar]
- Gronwald R. G., Grant F. J., Haldeman B. A., Hart C. E., O'Hara P. J., Hagen F. S., Ross R., Bowen-Pope D. F., Murray M. J. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class. Proc Natl Acad Sci U S A. 1988 May;85(10):3435–3439. doi: 10.1073/pnas.85.10.3435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gronwald R. G., Seifert R. A., Bowen-Pope D. F. Differential regulation of expression of two platelet-derived growth factor receptor subunits by transforming growth factor-beta. J Biol Chem. 1989 May 15;264(14):8120–8125. [PubMed] [Google Scholar]
- Jaffer F., Saunders C., Shultz P., Throckmorton D., Weinshell E., Abboud H. E. Regulation of mesangial cell growth by polypeptide mitogens. Inhibitory role of transforming growth factor beta. Am J Pathol. 1989 Aug;135(2):261–269. [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., Iida H., Alpers C. E., Majesky M. W., Schwartz S. M., Pritzi P., Gordon K., Gown A. M. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest. 1991 Mar;87(3):847–858. doi: 10.1172/JCI115089. [DOI] [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]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lee K. H., Bowen-Pope D. F., Reed R. R. Isolation and characterization of the alpha platelet-derived growth factor receptor from rat olfactory epithelium. Mol Cell Biol. 1990 May;10(5):2237–2246. doi: 10.1128/mcb.10.5.2237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leyva A., Jr, Kelley W. N. Measurement of DNA in cultured human cells. Anal Biochem. 1974 Nov;62(1):173–179. doi: 10.1016/0003-2697(74)90378-9. [DOI] [PubMed] [Google Scholar]
- Lovett D. H., Ryan J. L., Sterzel R. B. Stimulation of rat mesangial cell proliferation by macrophage interleukin 1. J Immunol. 1983 Dec;131(6):2830–2836. [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]
- Olivetti G., Anversa P., Melissari M., Loud A. V. Morphometry of the renal corpuscle during postnatal growth and compensatory hypertrophy. Kidney Int. 1980 Apr;17(4):438–454. doi: 10.1038/ki.1980.52. [DOI] [PubMed] [Google Scholar]
- Ratner L., Josephs S. F., Jarrett R., Reitz M. S., Jr, Wong-Staal F. Nucleotide sequence of transforming human c-sis cDNA clones with homology to platelet-derived growth factor. Nucleic Acids Res. 1985 Jul 25;13(14):5007–5018. doi: 10.1093/nar/13.14.5007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross R., Masuda J., Raines E. W., Gown A. M., Katsuda S., Sasahara M., Malden L. T., Masuko H., Sato H. Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science. 1990 May 25;248(4958):1009–1012. doi: 10.1126/science.2343305. [DOI] [PubMed] [Google Scholar]
- Ross R. Platelet-derived growth factor. Lancet. 1989 May 27;1(8648):1179–1182. doi: 10.1016/s0140-6736(89)92760-8. [DOI] [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]
- Yamamoto T., Wilson C. B. Complement dependence of antibody-induced mesangial cell injury in the rat. J Immunol. 1987 Jun 1;138(11):3758–3765. [PubMed] [Google Scholar]
- Yarden Y., Escobedo J. A., Kuang W. J., Yang-Feng T. L., Daniel T. O., Tremble P. M., Chen E. Y., Ando M. E., Harkins R. N., Francke U. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature. 1986 Sep 18;323(6085):226–232. doi: 10.1038/323226a0. [DOI] [PubMed] [Google Scholar]