Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Nov;143(5):1366–1376.

Temporal expression of autocrine growth factors corresponds to morphological features of mesangial proliferation in Habu snake venom-induced glomerulonephritis.

J L Barnes 1, H E Abboud 1
PMCID: PMC1887173  PMID: 8238253

Abstract

Habu snake venom induces an accelerated mesangial proliferative glomerulonephritis that follows a predictable course from early capillary aneurysms to micronodules comprised of confluent mesangial cells within 72 hours. We examined morphologically the course of mesangial cell proliferation and correlated it with the expression of messenger (m) RNA encoding two peptide growth factors, platelet-derived growth factor (PDGF) A and B chains and transforming growth factor-beta (TGF-beta). Rats were uninephrectomized and 24 hours later injected with Habu snake venom or saline. Kidney cortex and isolated glomeruli were obtained 24, 48, and 72 hours later for histological assessment, preparation and Northern analysis of mRNA, and immunohistochemical localization of PDGF using a polyclonal antibody that recognizes A and B chains. Maximal expression of PDGF B chain mRNA occurred at 24 hours and before the onset of mesangial cell proliferation; whereas maximal expression of PDGF A chain and TGF-beta mRNA occurred at 48 hours and during active mesangial cell proliferation. Expression of TGF-beta mRNA persisted at 72 hours at a time when PDGF A chain declined and PDGF B chain was not expressed compared to uninephrectomy and saline controls and at a time when mesangial cells within lesions reached confluence and proliferation subsided. PDGF protein localized in glomerular lesions associated with platelets at 24 and 48 hours and within mesangial cells at 48 and 72 hours. These results agree with the known roles of PDGF and TGF-beta as positive and negative modulators, respectively, of mesangial cell growth in vitro and suggest that a relative balance of the expression of these factors may operate in glomerular disease in vivo.

Full text

PDF
1366

Images in this article

1368Figure 1
on p.1368
1370Figure 2
on p.1370
1371Figure 3
on p.1371
1372Figure 4
on p.1372
1373Figure 6
on p.1373

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abboud H. E. Platelet-derived growth factor and mesangial cells. Kidney Int. 1992 Mar;41(3):581–583. doi: 10.1038/ki.1992.86. [DOI] [PubMed] [Google Scholar]
  2. Abboud H. E., Poptic E., DiCorleto P. Production of platelet-derived growth factorlike protein by rat mesangial cells in culture. J Clin Invest. 1987 Sep;80(3):675–683. doi: 10.1172/JCI113121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnes J. L. Amelioration of habu venom-induced glomerular lesions: potential role for platelet secretory proteins. J Lab Clin Med. 1989 Aug;114(2):200–206. [PubMed] [Google Scholar]
  4. Barnes J. L. Glomerular localization of platelet secretory proteins in mesangial proliferative lesions induced by habu snake venom. J Histochem Cytochem. 1989 Jul;37(7):1075–1082. doi: 10.1177/37.7.2659663. [DOI] [PubMed] [Google Scholar]
  5. Barnes J. L., Hevey K. A. Glomerular mesangial cell migration in response to platelet-derived growth factor. Lab Invest. 1990 Mar;62(3):379–382. [PubMed] [Google Scholar]
  6. Barnes J. L., Hevey K. A. Glomerular mesangial cell migration. Response to platelet secretory products. Am J Pathol. 1991 Apr;138(4):859–866. [PMC free article] [PubMed] [Google Scholar]
  7. Barnes J. L., Venkatachalam M. A. The role of platelets and polycationic mediators in glomerular vascular injury. Semin Nephrol. 1985 Mar;5(1):57–68. [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Bowen-Pope D. F., Hart C. E., Seifert R. A. Sera and conditioned media contain different isoforms of platelet-derived growth factor (PDGF) which bind to different classes of PDGF receptor. J Biol Chem. 1989 Feb 15;264(5):2502–2508. [PubMed] [Google Scholar]
  11. Cattell V., Bradfield J. W. Focal mesangial proliferative glomerulonephritis in the rat caused by habu snake venom. A morphologic study. Am J Pathol. 1977 Jun;87(3):511–524. [PMC free article] [PubMed] [Google Scholar]
  12. Cattell V. Focal mesangial proliferative glomerulonephritis in the rat caused by Habu snake venom: the role of platelets. Br J Exp Pathol. 1979 Apr;60(2):201–208. [PMC free article] [PubMed] [Google Scholar]
  13. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  14. Coimbra T., Wiggins R., Noh J. W., Merritt S., Phan S. H. Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit. Am J Pathol. 1991 Jan;138(1):223–234. [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Fine L. G., Hammerman M. R., Abboud H. E. Evolving role of growth factors in the renal response to acute and chronic disease. J Am Soc Nephrol. 1992 Jan;2(7):1163–1170. doi: 10.1681/ASN.V271163. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. Johnson R. J. Platelets in inflammatory glomerular injury. Semin Nephrol. 1991 May;11(3):276–284. [PubMed] [Google Scholar]
  23. KRAKOWER C. A., GREENSPON S. A. Localization of the nephrotoxic antigen within the isolated renal glomerulus. AMA Arch Pathol. 1951 Jun;51(6):629–639. [PubMed] [Google Scholar]
  24. Kaname S., Uchida S., Ogata E., Kurokawa K. Autocrine secretion of transforming growth factor-beta in cultured rat mesangial cells. Kidney Int. 1992 Dec;42(6):1319–1327. doi: 10.1038/ki.1992.423. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Mercola M., Wang C. Y., Kelly J., Brownlee C., Jackson-Grusby L., Stiles C., Bowen-Pope D. Selective expression of PDGF A and its receptor during early mouse embryogenesis. Dev Biol. 1990 Mar;138(1):114–122. doi: 10.1016/0012-1606(90)90181-h. [DOI] [PubMed] [Google Scholar]
  27. Nakajima M., Hewitson T. D., Mathews D. C., Kincaid-Smith P. Platelet-derived growth factor mesangial deposits in mesangial IgA glomerulonephritis. Nephrol Dial Transplant. 1991;6(1):11–16. doi: 10.1093/ndt/6.1.11. [DOI] [PubMed] [Google Scholar]
  28. Nakamura T., Miller D., Ruoslahti E., Border W. A. Production of extracellular matrix by glomerular epithelial cells is regulated by transforming growth factor-beta 1. Kidney Int. 1992 May;41(5):1213–1221. doi: 10.1038/ki.1992.183. [DOI] [PubMed] [Google Scholar]
  29. Newman P. J., Derbes R. S., Aster R. H. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest. 1989 May;83(5):1778–1781. doi: 10.1172/JCI114082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Okuda S., Languino L. R., Ruoslahti E., Border W. A. Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. J Clin Invest. 1990 Aug;86(2):453–462. doi: 10.1172/JCI114731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Roberts A. B., Flanders K. C., Heine U. I., Jakowlew S., Kondaiah P., Kim S. J., Sporn M. B. Transforming growth factor-beta: multifunctional regulator of differentiation and development. Philos Trans R Soc Lond B Biol Sci. 1990 Mar 12;327(1239):145–154. doi: 10.1098/rstb.1990.0050. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Sottile J., Mosher D. F., Fullenweider J., George J. N. Human platelets contain mRNA transcripts for platelet factor 4 and actin. Thromb Haemost. 1989 Dec 29;62(4):1100–1102. [PubMed] [Google Scholar]
  35. 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]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES