Abstract
Both PDGF and IL-1 play important roles as autocrine growth factors for cultured mesangial cells, and may be closely associated with the progression of glomerulonephritis. In this study we investigated intraglomerular expressions of PDGF-B and IL-1 alpha mRNA in mice with bovine serum albumin (BSA) nephritis, a model of immune complex-mediated glomerulonephritis, using the reverse transcription-polymerase chain reaction (RT-PCR) method. We also quantified intraglomerular PDGF-B mRNA by the competitive PCR and studied the correlation between the level of intraglomerular PDGF-B mRNA expression and the degree of observed glomerular injury. While expression of neither PDGF-B nor IL-1 alpha mRNA was detected in glomeruli from control mice, both were strongly expressed in glomeruli from mice with BSA nephritis. IL-1 alpha mRNA in glomeruli showed low accumulation in mice with mild glomerular injury, and was increased in mice with moderate glomerular injury. In contrast, high intraglomerular expression of PDGF-B mRNA occurred in all mice with mild glomerular injury and continued throughout the course of the disease. We observed no correlation between the level of PDGF-B mRNA expression and the histologic grade of renal damage. These results suggest that PDGF and IL-1 have different growth properties, and PDGF might play a role as a competence factor rather than a progression factor in the pathogenesis of immune complex-mediated glomerulonephritis.
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- 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]
- Bonthron D. T., Sultan P., Collins T. Structure of the murine c-sis proto-oncogene (Sis, PDGFB) encoding the B chain of platelet-derived growth factor. Genomics. 1991 May;10(1):287–292. doi: 10.1016/0888-7543(91)90515-g. [DOI] [PubMed] [Google Scholar]
- Bywater M., Rorsman F., Bongcam-Rudloff E., Mark G., Hammacher A., Heldin C. H., Westermark B., Betsholtz C. Expression of recombinant platelet-derived growth factor A- and B-chain homodimers in rat-1 cells and human fibroblasts reveals differences in protein processing and autocrine effects. Mol Cell Biol. 1988 Jul;8(7):2753–2762. doi: 10.1128/mcb.8.7.2753. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen X. M., Hiki Y., Aozuka S., Kobayashi Y. [Bovine serum albumin (BSA) nephritis in mice--its induction and immunoserological analysis]. Nihon Jinzo Gakkai Shi. 1987 Feb;29(2):123–136. [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Daniel T. O., Gibbs V. C., Milfay D. F., Garovoy M. R., Williams L. T. Thrombin stimulates c-sis gene expression in microvascular endothelial cells. J Biol Chem. 1986 Jul 25;261(21):9579–9582. [PubMed] [Google Scholar]
- Deuel T. F., Pierce G. F., Yeh H. J., Shawver L. K., Milner P. G., Kimura A. Platelet-derived growth factor/sis in normal and neoplastic cell growth. J Cell Physiol Suppl. 1987;Suppl 5:95–99. doi: 10.1002/jcp.1041330418. [DOI] [PubMed] [Google Scholar]
- DiCorleto P. E., Bowen-Pope D. F. Cultured endothelial cells produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1919–1923. doi: 10.1073/pnas.80.7.1919. [DOI] [PMC free article] [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]
- 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]
- 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]
- Gilliland G., Perrin S., Blanchard K., Bunn H. F. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2725–2729. doi: 10.1073/pnas.87.7.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hosang M. Suramin binds to platelet-derived growth factor and inhibits its biological activity. J Cell Biochem. 1985;29(3):265–273. doi: 10.1002/jcb.240290310. [DOI] [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]
- Iwano M., Dohi K., Hirata E., Horii Y., Shiiki H., Ishikawa H. Induction of interleukin 6 synthesis in mouse glomeruli and cultured mesangial cells. Nephron. 1992;62(1):58–65. doi: 10.1159/000186996. [DOI] [PubMed] [Google Scholar]
- Johnson R. J., Raines E. W., Floege J., Yoshimura A., Pritzl P., Alpers C., Ross R. Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor. J Exp Med. 1992 May 1;175(5):1413–1416. doi: 10.1084/jem.175.5.1413. [DOI] [PMC free article] [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]
- Mendoza A. E., Young R., Orkin S. H., Collins T. Increased platelet-derived growth factor A-chain expression in human uterine smooth muscle cells during the physiologic hypertrophy of pregnancy. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2177–2181. doi: 10.1073/pnas.87.6.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray L. J., Lee R., Martens C. In vivo cytokine gene expression in T cell subsets of the autoimmune MRL/Mp-lpr/lpr mouse. Eur J Immunol. 1990 Jan;20(1):163–170. doi: 10.1002/eji.1830200124. [DOI] [PubMed] [Google Scholar]
- Nistér M., Hammacher A., Mellström K., Siegbahn A., Rönnstrand L., Westermark B., Heldin C. H. A glioma-derived PDGF A chain homodimer has different functional activities from a PDGF AB heterodimer purified from human platelets. Cell. 1988 Mar 25;52(6):791–799. doi: 10.1016/0092-8674(88)90421-7. [DOI] [PubMed] [Google Scholar]
- Pardee A. B., Coppock D. L., Yang H. C. Regulation of cell proliferation at the onset of DNA synthesis. J Cell Sci Suppl. 1986;4:171–180. doi: 10.1242/jcs.1986.supplement_4.11. [DOI] [PubMed] [Google Scholar]
- Rappolee D. A., Wang A., Mark D., Werb Z. Novel method for studying mRNA phenotypes in single or small numbers of cells. J Cell Biochem. 1989 Jan;39(1):1–11. doi: 10.1002/jcb.240390102. [DOI] [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]
- Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
- Scher C. D., Shepard R. C., Antoniades H. N., Stiles C. D. Platelet-derived growth factor and the regulation of the mammalian fibroblast cell cycle. Biochim Biophys Acta. 1979 Aug 10;560(2):217–241. doi: 10.1016/0304-419x(79)90020-9. [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]
- Tong B. D., Auer D. E., Jaye M., Kaplow J. M., Ricca G., McConathy E., Drohan W., Deuel T. F. cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains. Nature. 1987 Aug 13;328(6131):619–621. doi: 10.1038/328619a0. [DOI] [PubMed] [Google Scholar]
- Wang A. M., Doyle M. V., Mark D. F. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9717–9721. doi: 10.1073/pnas.86.24.9717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilcox J. N., Smith K. M., Williams L. T., Schwartz S. M., Gordon D. Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. J Clin Invest. 1988 Sep;82(3):1134–1143. doi: 10.1172/JCI113671. [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]