Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Sep 15;88(18):8159–8163. doi: 10.1073/pnas.88.18.8159

Neurotrophic activity of platelet-derived growth factor (PDGF): Rat neuronal cells possess functional PDGF beta-type receptors and respond to PDGF.

A Smits 1, M Kato 1, B Westermark 1, M Nistér 1, C H Heldin 1, K Funa 1
PMCID: PMC52466  PMID: 1654560

Abstract

The different isoforms of PDGF bind with different affinities to two different receptor types. Previously, these receptors have been demonstrated mainly on mesenchymal and glial cells. We show here that PDGF beta-type receptors are present also on rat brain neurons in vivo as well as in vitro. Immunohistochemical analysis of a sequentially sectioned brain of a newborn rat revealed the presence of PDGF beta receptors in neurons throughout the central nervous system. These beta-receptor-bearing cells were shown to contain neurofilaments by double immunofluorescence staining. Furthermore, the PDGF-BB isoform bound to cells in a neuron-enriched culture from newborn rat brains and induced c-Fos protein in these cells. Continuous PDGF-BB treatment of primary rat brain cell cultures resulted in outgrowth of neurites and prolonged survival. These results indicate a neurotrophic effect of PDGF-BB.

Full text

PDF
8159

Images in this article

Selected References

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

  1. Bishayee S., Majumdar S., Khire J., Das M. Ligand-induced dimerization of the platelet-derived growth factor receptor. Monomer-dimer interconversion occurs independent of receptor phosphorylation. J Biol Chem. 1989 Jul 15;264(20):11699–11705. [PubMed] [Google Scholar]
  2. Claesson-Welsh L., Eriksson A., Westermark B., Heldin C. H. cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4917–4921. doi: 10.1073/pnas.86.13.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Debus E., Weber K., Osborn M. Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides. Differentiation. 1983;25(2):193–203. doi: 10.1111/j.1432-0436.1984.tb01355.x. [DOI] [PubMed] [Google Scholar]
  5. Hart C. E., Forstrom J. W., Kelly J. D., Seifert R. A., Smith R. A., Ross R., Murray M. J., Bowen-Pope D. F. Two classes of PDGF receptor recognize different isoforms of PDGF. Science. 1988 Jun 10;240(4858):1529–1531. doi: 10.1126/science.2836952. [DOI] [PubMed] [Google Scholar]
  6. Hartikka J., Hefti F. Development of septal cholinergic neurons in culture: plating density and glial cells modulate effects of NGF on survival, fiber growth, and expression of transmitter-specific enzymes. J Neurosci. 1988 Aug;8(8):2967–2985. doi: 10.1523/JNEUROSCI.08-08-02967.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Heldin C. H., Bäckström G., Ostman A., Hammacher A., Rönnstrand L., Rubin K., Nistér M., Westermark B. Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types. EMBO J. 1988 May;7(5):1387–1393. doi: 10.1002/j.1460-2075.1988.tb02955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heldin C. H., Ernlund A., Rorsman C., Rönnstrand L. Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation. J Biol Chem. 1989 May 25;264(15):8905–8912. [PubMed] [Google Scholar]
  9. Heldin C. H., Westermark B. Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell Regul. 1990 Jul;1(8):555–566. doi: 10.1091/mbc.1.8.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hohn A., Leibrock J., Bailey K., Barde Y. A. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990 Mar 22;344(6264):339–341. doi: 10.1038/344339a0. [DOI] [PubMed] [Google Scholar]
  11. Kruijer W., Schubert D., Verma I. M. Induction of the proto-oncogene fos by nerve growth factor. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7330–7334. doi: 10.1073/pnas.82.21.7330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masiakowski P., Thoenen H., Barde Y. A. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989 Sep 14;341(6238):149–152. doi: 10.1038/341149a0. [DOI] [PubMed] [Google Scholar]
  13. Matsui T., Heidaran M., Miki T., Popescu N., La Rochelle W., Kraus M., Pierce J., Aaronson S. Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989 Feb 10;243(4892):800–804. doi: 10.1126/science.2536956. [DOI] [PubMed] [Google Scholar]
  14. Mercola M., Melton D. A., Stiles C. D. Platelet-derived growth factor A chain is maternally encoded in Xenopus embryos. Science. 1988 Sep 2;241(4870):1223–1225. doi: 10.1126/science.3413486. [DOI] [PubMed] [Google Scholar]
  15. Morrison R. S., Kornblum H. I., Leslie F. M., Bradshaw R. A. Trophic stimulation of cultured neurons from neonatal rat brain by epidermal growth factor. Science. 1987 Oct 2;238(4823):72–75. doi: 10.1126/science.3498986. [DOI] [PubMed] [Google Scholar]
  16. Noble M., Murray K., Stroobant P., Waterfield M. D., Riddle P. Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature. 1988 Jun 9;333(6173):560–562. doi: 10.1038/333560a0. [DOI] [PubMed] [Google Scholar]
  17. Ostman A., Bäckström G., Fong N., Betsholtz C., Wernstedt C., Hellman U., Westermark B., Valenzuela P., Heldin C. H. Expression of three recombinant homodimeric isoforms of PDGF in Saccharomyces cerevisiae: evidence for difference in receptor binding and functional activities. Growth Factors. 1989;1(3):271–281. doi: 10.3109/08977198908998003. [DOI] [PubMed] [Google Scholar]
  18. Pringle N., Collarini E. J., Mosley M. J., Heldin C. H., Westermark B., Richardson W. D. PDGF A chain homodimers drive proliferation of bipotential (O-2A) glial progenitor cells in the developing rat optic nerve. EMBO J. 1989 Apr;8(4):1049–1056. doi: 10.1002/j.1460-2075.1989.tb03472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Raff M. C. Glial cell diversification in the rat optic nerve. Science. 1989 Mar 17;243(4897):1450–1455. doi: 10.1126/science.2648568. [DOI] [PubMed] [Google Scholar]
  20. Raff M. C., Lillien L. E., Richardson W. D., Burne J. F., Noble M. D. Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature. 1988 Jun 9;333(6173):562–565. doi: 10.1038/333562a0. [DOI] [PubMed] [Google Scholar]
  21. Raizada M. K., Morse C. A., Gonzales R. A., Crews F. T., Sumners C. Receptors for phorbol esters are primarily localized in neurons: comparison of neuronal and glial cultures. Neurochem Res. 1988 Jan;13(1):51–56. doi: 10.1007/BF00971854. [DOI] [PubMed] [Google Scholar]
  22. Richardson W. D., Pringle N., Mosley M. J., Westermark B., Dubois-Dalcq M. A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell. 1988 Apr 22;53(2):309–319. doi: 10.1016/0092-8674(88)90392-3. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Sasahara M., Fries J. W., Raines E. W., Gown A. M., Westrum L. E., Frosch M. P., Bonthron D. T., Ross R., Collins T. PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model. Cell. 1991 Jan 11;64(1):217–227. doi: 10.1016/0092-8674(91)90223-l. [DOI] [PubMed] [Google Scholar]
  25. Seifert R. A., Hart C. E., Phillips P. E., Forstrom J. W., Ross R., Murray M. J., Bowen-Pope D. F. Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem. 1989 May 25;264(15):8771–8778. [PubMed] [Google Scholar]
  26. Smits A., Hermansson M., Nistér M., Karnushina I., Heldin C. H., Westermark B., Funa K. Rat brain capillary endothelial cells express functional PDGF B-type receptors. Growth Factors. 1989;2(1):1–8. doi: 10.3109/08977198909069076. [DOI] [PubMed] [Google Scholar]
  27. Sonnenberg J. L., Rauscher F. J., 3rd, Morgan J. I., Curran T. Regulation of proenkephalin by Fos and Jun. Science. 1989 Dec 22;246(4937):1622–1625. doi: 10.1126/science.2512642. [DOI] [PubMed] [Google Scholar]
  28. Sprugel K. H., McPherson J. M., Clowes A. W., Ross R. Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. Am J Pathol. 1987 Dec;129(3):601–613. [PMC free article] [PubMed] [Google Scholar]
  29. Walicke P. A. Novel neurotrophic factors, receptors, and oncogenes. Annu Rev Neurosci. 1989;12:103–126. doi: 10.1146/annurev.ne.12.030189.000535. [DOI] [PubMed] [Google Scholar]
  30. Wang J. L., Nistér M., Hermansson M., Westermark B., Pontén J. Expression of PDGF beta-receptors in human meningioma cells. Int J Cancer. 1990 Nov 15;46(5):772–778. doi: 10.1002/ijc.2910460504. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Yeh H. J., Ruit K. G., Wang Y. X., Parks W. C., Snider W. D., Deuel T. F. PDGF A-chain gene is expressed by mammalian neurons during development and in maturity. Cell. 1991 Jan 11;64(1):209–216. doi: 10.1016/0092-8674(91)90222-k. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES