Alternative titles; symbols
HGNC Approved Gene Symbol: PDGFA
Cytogenetic location: 7p22.3 Genomic coordinates (GRCh38): 7:497,258-520,700 (from NCBI)
Human platelet-derived growth factor (PDGF) is a cationic glycoprotein consisting of homo- or heterodimers of polypeptide chains A and/or B (PDGFB; 190040). It is a potent mitogen for connective tissue cells and exerts its function by interacting with 2 related receptor tyrosine kinases, PDGFRA (173490) and PDGFRB (173410) (see Bonthron et al. (1988) and Bostrom et al. (1996)).
Betsholtz et al. (1986) isolated the PDGFA nucleotide sequence from a human glioma cDNA library. The 1.3-kb clone was predicted to encode a 211-amino acid precursor protein that was found to share 40% homology with the PDGFB protein Northern blot analysis revealed 3 transcripts of 1.9, 2.3 and 2.8 kb.
Bonthron et al. (1988) determined that the PDGFA gene contains 7 exons spanning about 24 kilobases.
By somatic cell hybrid analysis, Betsholtz et al. (1986) mapped the PDGFA gene to 7pter-q22. Bonthron et al. (1988) localized the PDGFA gene to 7p22-p21 by in situ hybridization.
Stenman et al. (1988) obtained conflicting results on the localization of PDGFA. By in situ hybridization, they assigned the gene to 7q11.23. The controversy was resolved by Bonthron et al. (1992), who performed nonisotopic in situ hybridization using new genomic PDGFA subclones and analyzed somatic cell hybrid DNAs for the presence of human PDGFA by PCR. By both in situ hybridization and analysis of an unusual minisatellite in IVS4, they showed that PDGFA is outside the monosomic region in a patient with a de novo deletion, del(7)(pter-p22.1). They suggested that PDGFA is located either just proximal to the breakpoint at 7p22.1 or, perhaps more likely in view of the cytogenetic appearance in which the PDGFA hybridization spots are at the extreme tip of 7p, within a telomeric segment of 7p retained in the patient with the deletion. Stenman et al. (1992) subsequently assigned the gene to 7p22 by a combination of in situ hybridization and human/mouse somatic cell hybrid studies.
Beckmann et al. (1988) compared the biologic properties and transforming potential of the 2 PDGF chains.
By in situ hybridization, Wilcox et al. (1988) demonstrated PDGF A and B chain mRNA in mesenchymal-appearing intimal cells and endothelial cells, respectively, of atherosclerotic plaques. Furthermore, they found that PDGF receptor (see PDGFRA; 173490) mRNA was localized predominantly in the plaque intima.
Bostrom et al. (1996) showed that homozygous Pdgfa-null mice die either prenatally before E10 or postnatally before age 6 weeks. Postnatally surviving Pdgfa-null mice developed lung emphysema secondary to failure of alveolar septation caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. There was a symmetrical reduction in the size of most other organs, with no other obvious pathologic signs.
Gnessi et al. (2000) found that Pdgfa-deficient male mice developed progressive reduction in testicular size, Leydig cell loss, and spermatogenic arrest. In older Pdgfa-deficient mice, circulating testosterone was not detectable, confirming that spermatogenic arrest was mediated by testosterone deficiency in Pdgfa-deficient animals. Immunohistochemistry and in situ hybridization analysis showed that normal mice express Pdgfa and Pdgfra in seminiferous epithelium and interstitial mesenchymal cells, respectively. The findings suggested that Leydig cells arise from PDGFRA-positive progenitors.
Beckmann, M. P., Betsholtz, C., Heldin, C.-H., Westermark, B., Di Marco, E., Di Fiore, P. P., Robbins, K. C., Aaronson, S. A. Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains. Science 241: 1346-1349, 1988. [PubMed: 2842868] [Full Text: https://doi.org/10.1126/science.2842868]
Betsholtz, C., Johnsson, A., Heldin, C.-H., Westermark, B., Lind, P., Urdea, M. S., Eddy, R., Shows, T. B., Philpott, K., Mellor, A. L., Knott, T. J., Scott, J. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature 320: 695-699, 1986. [PubMed: 3754619] [Full Text: https://doi.org/10.1038/320695a0]
Bonthron, D., Collins, T., Grzeschik, K.-H., van Roy, N., Speleman, F. Platelet-derived growth factor A chain: confirmation of localization of PDGFA to chromosome 7p22 and description of an unusual minisatellite. Genomics 13: 257-263, 1992. [PubMed: 1612586] [Full Text: https://doi.org/10.1016/0888-7543(92)90240-s]
Bonthron, D. T., Morton, C. C., Orkin, S. H., Collins, T. Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing. Proc. Nat. Acad. Sci. 85: 1492-1496, 1988. [PubMed: 3422746] [Full Text: https://doi.org/10.1073/pnas.85.5.1492]
Bostrom, H., Willetts, K., Pekny, M., Leveen, P., Lindahl, P., Hedstrand, H., Pekna, M., Hellstrom, M., Gebre-Medhin, S., Schalling, M., Nilsson, M., Kurland, S., Tornell, J., Heath, J. K., Betsholtz, C. PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis. Cell 85: 863-873, 1996. [PubMed: 8681381] [Full Text: https://doi.org/10.1016/s0092-8674(00)81270-2]
Gnessi, L., Basciani, S., Mariani, S., Arizzi, M., Spera, G., Wang, C., Bondjers, C., Karlsson, L., Betsholtz, C. Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice. J. Cell Biol. 149: 1019-1025, 2000. [PubMed: 10831606] [Full Text: https://doi.org/10.1083/jcb.149.5.1019]
Rorsman, F., Bywater, M., Knott, T. J., Scott, J., Betsholtz, C. Structural characterization of the human platelet-derived growth factor A-chain cDNA and gene: alternative exon usage predicts two different precursor proteins. Molec. Cell. Biol. 8: 571-577, 1988. [PubMed: 2832727] [Full Text: https://doi.org/10.1128/mcb.8.2.571-577.1988]
Stenman, G., Rorsman, F., Betsholtz, C. Sublocalization of the human PDGF A-chain gene to chromosome 7, band q11.23, by in situ hybridization. Exp. Cell Res. 178: 180-184, 1988. [PubMed: 3409978] [Full Text: https://doi.org/10.1016/0014-4827(88)90389-8]
Stenman, G., Rorsman, F., Huebner, K., Betsholtz, C. The human platelet-derived growth factor alpha chain (PDGFA) gene maps to chromosome 7p22. Cytogenet. Cell Genet. 60: 206-207, 1992. [PubMed: 1505216] [Full Text: https://doi.org/10.1159/000133337]
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. 82: 1134-1143, 1988. [PubMed: 2843568] [Full Text: https://doi.org/10.1172/JCI113671]