Role of platelet-derived growth factors in physiology and medicine.

By Johanna Andrae, R. Gallini, C. Betsholtz. Genes & Development, 2008

2,354 citations recorded by the source corpus.

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-alpha 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-beta 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.

Subfields: Molecular Biology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/2cd3f49cdb58a0d5f9a14ad224b8e254cfc971b7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Berislav Zlokovic
2. R. Bell
3. E. Winkler
4. A. Armulik
5. G. Genové
6. Xiumin Wu
7. Cuiling Zhong
8. N. Ferrara

In Rheumatology

1. M. C. Brotons
2. J. Yarnold

Citations in the corpus

• In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high fat feeding (2012, neutral): “C PDGFRa progenitors are found in numerous tissues where they appear to be involved in cellular repair and restoration (Andrae et al., 2008; Hoch and Soriano, 2003).”
• PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. (2009, background): “PDGF-C signaling through PDGF receptor (PDGFR) a and b homo-or heterodimers is important for the development of connective tissues and for wound healing (Andrae et al., 2008; Li et al., SIGNIFICANCE Tumor-associated fibroblasts (TAFs) are active players in tumorigenesis.”
• Platelet secretion: From haemostasis to wound healing and beyond (2015, background): “Subsequently approaches targeting the PDGF signalling pathway developed but despite promise in animal models, PDGF inhibition has not yet shown to be effective in humans [88].”
• FGF/FGFR signaling in health and disease (2020, background): “PDGFRmediated signaling can regulate cell motility, proliferation, angiogenesis, and are involved in a range of diseases.(80) In vitro and in vivo experiments revealed that both PDGFRα and PDGFRβ interact with high affinity with FGFR1.”
• Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. (2011, background): “However, as discussed above, PDGFRb is also expressed by certain fibroblasts (Andrae et al., 2008; Heldin and Westermark, 1999), and it is therefore still not entirely clear whether perivascular mesenchymal stem or progenitor cells expressing PDGFRb derive from pericytes proper, or from, e.g.,…”
• Tumor angiogenesis and vascular normalization: alternative therapeutic targets (2017, background): “endothelial vessels by heparan sulfate proteoglycans, where it serves as an attractant for comigrating pericytes expressing the receptor-b (PDGFRb) [27].”
• Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle (2011, background): “Along with TGF-b, signaling between PDGFs and PDGFRs is also considered to be involved in several fibrotic diseases (Andrae et al., 2008).”
• Pathogenetic mechanisms in radiation fibrosis. (2010, background): “As well as the TGFb1/Smad and TGFb1/rho/JNK pathways, other signalling cascades have been linked to fibrosis including PDGF/ PDGFR, IGF/IGFR, EGF/EGFR, TNF-a and FGF-2 [52].”
• Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex (2010, methodology): “PDGFRα signaling controls gastrulation and the development of many organs, including lung, intestine, skin, testis, kidney, skeleton, and neuroprotective tissues, whereas PDGFRβ signaling has been well established in early hematopoiesis and blood vessel formation (3).”
• Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle (2010, background): “Particularly strong expression of PDGFRα has been observed in subtypes of mesenchymal progenitor cells and oligodendrocyte progenitors, and PDGF-A–PDGFRα signalling appears to regulate a broad range of progenitor cells in several developmental processe”
• Central nervous system pericytes in health and disease (2011, background): “After secretion, a positively charged C terminal sequence within each PDGF-B monomer termed the retention motif electrostatically interacts with negatively charged heparin sulfate proteoglycans contained within the extracellular matrix, leading to localized PDGF-BB retentio”