Role of platelet-derived growth factors in physiology and medicine

  1. Johanna Andrae1,2,
  2. Radiosa Gallini1, and
  3. Christer Betsholtz1,2,3,4
  1. 1 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
  2. 2 Ludwig Institute for Cancer Research, Stockholm Branch, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
  3. 3 Department of Medicine, Karolinska Institutet, SE 171 77 Stockholm, Sweden

Abstract

Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have served as prototypes for growth factor and receptor tyrosine kinase function for more than 25 years. Studies of PDGFs and PDGFRs in animal development have revealed roles for PDGFR-α signaling in gastrulation and in the development of the cranial and cardiac neural crest, gonads, lung, intestine, skin, CNS, and skeleton. Similarly, roles for PDGFR-β signaling have been established in blood vessel formation and early hematopoiesis. PDGF signaling is implicated in a range of diseases. Autocrine activation of PDGF signaling pathways is involved in certain gliomas, sarcomas, and leukemias. Paracrine PDGF signaling is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial–mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological mesenchymal responses in vascular disorders such as atherosclerosis, restenosis, pulmonary hypertension, and retinal diseases, as well as in fibrotic diseases, including pulmonary fibrosis, liver cirrhosis, scleroderma, glomerulosclerosis, and cardiac fibrosis. We review basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts.

Keywords

Footnotes

  • 4 Corresponding author.

    4 E-MAIL christer.betsholtz{at}ki.se; FAX 46-8-313445.

  • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1653708.

  • Freely available online through the Genes & Development Open Access option.

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