Platelet Derived Growth FactorEdit
Platelet Derived Growth Factor (PDGF), also known as Platelet Derived Growth Factor, is a family of mitogenic signaling proteins that regulate the growth, survival, and migration of mesenchymal cells. PDGF is produced by platelets and by several other cell types, and it functions through specific cell-surface receptors to coordinate processes such as development, tissue repair, and remodeling of connective tissue. As a key component of the broader growth-factor network, PDGF interacts with other signals to shape how tissues regenerate after injury and how fibrous tissue forms in chronic disease. In medicine, PDGF signaling has been exploited both as a therapeutic target and as a therapeutic agent in wound care. Growth factors Cell signaling Wound healing Angiogenesis
History and discovery
The PDGF story begins with observations that platelets release potent signals capable of stimulating the growth of connective tissue cells. Over the following decades, researchers identified multiple PDGF polypeptides and demonstrated that they form active dimers and engage with specific receptors on target cells. This work established a canonical signaling system in which distinct PDGF ligands bind to complementary receptor tyrosine kinases, triggering cascades that drive proliferation and migration in mesenchymal lineages. Today, the main PDGF ligands are commonly referred to as PDGF-A, PDGF-B, PDGF-C, and PDGF-D, which can assemble into various homo- and heterodimers to exert nuanced effects in different tissues. PDGF-A PDGF-B PDGF-C PDGF-D PDGF receptor PDGF receptor
Structure and signaling
PDGF ligands are dimers that bind to two receptor tyrosine kinases, PDGFR-α and PDGFR-β. Receptor assembly and autophosphorylation activate downstream signaling pathways, including the PI3K/Akt and Ras/MAPK cascades, as well as PLCγ signaling. These pathways regulate cell cycle progression, cytoskeletal dynamics, and survival, enabling mesenchymal cells such as fibroblasts, smooth muscle cells, and pericytes to proliferate and migrate in response to injury or developmental cues. The receptor–ligand system exhibits specificity and redundancy: different PDGF dimers preferentially engage PDGFR-α, PDGFR-β, or both, allowing context-dependent control of cell behavior. Receptor tyrosine kinases PI3K MAPK signaling pathway Ras-MAPK Fibroblast Pericyte
Physiological roles
Development: PDGF signaling guides the migration and proliferation of mesenchymal progenitors during organogenesis, contributing to the formation of connective tissue, vasculature, and supporting stroma. The coordination of PDGF signals with other growth factors ensures proper tissue architecture and function. Developmental biology Vasculature
Wound healing and tissue repair: In response to vascular injury, platelets release PDGF and other mitogens that recruit fibroblasts and promote extracellular matrix deposition, facilitating wound closure and scar formation. PDGF also supports the maturation of blood vessels by recruiting pericytes. Wound healing Fibroblast Angiogenesis
Angiogenesis and vascular remodeling: PDGF stimulates perivascular cells and fibroblasts that partner with endothelial cells to stabilize and remodel new vessels, contributing to tissue renewal and repair. Angiogenesis Blood vessel
Fibrosis and remodeling: Abnormal PDGF signaling can contribute to fibrotic diseases where excessive connective tissue deposition leads to organ dysfunction. Research continues to delineate when PDGF promotes beneficial repair versus pathological scarring. Fibrosis
Clinical significance
Therapeutic applications: A well-known clinical use of PDGF is in wound care. Becaplermin (PDGF-BB) gel is approved for certain diabetic foot ulcers, where topical PDGF-BB promotes healing in select patients. The therapy illustrates how a growth factor can be repurposed to enhance tissue repair, though it requires careful patient selection and monitoring. Becaplermin Diabetic foot ulcer
Cancer and fibrotic disease targets: PDGF signaling participates in the tumor microenvironment, with stromal cells and certain tumor cells responding to PDGF cues. Inhibitors that target PDGFR signaling are part of the broader class of tyrosine kinase inhibitors used in cancer therapy, particularly for tumors with autocrine or paracrine PDGF signaling. The use of these inhibitors highlights the balance between therapeutic benefit and potential impacts on normal tissue homeostasis. Cancer Tyrosine kinase inhibitors PDGFR-α PDGFR-β
Safety and regulatory considerations: As with any growth-factor–based therapy, efficacy must be weighed against safety concerns. In some cases, high-dose PDGF therapies or broad interference with growth-factor signaling can raise concerns about inappropriate tissue proliferation or effects on distant tissues. Regulatory agencies emphasize appropriate indications and monitoring in clinical use, and ongoing research seeks to optimize dosing, delivery, and patient selection. Regulatory affairs Clinical trials
Controversies and scientific debates
PDGF signaling sits at the intersection of fundamental biology and translational medicine, and as such invites discussion about biology’s redundancy and the proper use of growth factors in therapy. Proponents of targeted PDGFR inhibition point to the potential to limit tumor stromal support and fibrosis, while opponents caution that signaling networks are highly interconnected; blocking PDGF pathways can lead to compensatory changes in other growth-factor systems. In wound care and regenerative medicine, debates focus on patient selection, cost, and long-term outcomes, as well as the balance between short-term healing benefits and the risks of stimulating cell proliferation in anatomically sensitive regions. Signaling networks Fibrosis Cancer therapy