Platelet-Derived Growth Factor-BB (PDGF-BB) stands out as a pivotal signaling molecule with diverse roles in various cellular processes (1). This review delves into the multifaceted nature of PDGF-BB, shedding light on its mechanisms of action, physiological functions, and implications across different biological contexts. The intricate interplay of PDGF-BB in cell proliferation, migration, angiogenesis, and tissue repair underscores its significance in both health and disease.
Mechanisms of Action
PDGF-BB, a member of the PDGF family, exerts its biological effects primarily through binding to two receptor types: PDGF receptor alpha (PDGFRα) and PDGF receptor beta (PDGFRβ) (2). This duality in receptor specificity leads to a range of downstream signaling events. Upon ligand binding, receptor dimerization occurs, followed by autophosphorylation and activation of intracellular kinases, such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. These cascades collectively regulate cellular processes, including gene expression, cytoskeletal rearrangement, and survival.
Cellular Proliferation and Migration
PDGF-BB's role as a potent mitogen underscores its contribution to cellular proliferation (3). The activation of PDGFRs stimulates DNA synthesis and cell cycle progression, driving cell division. In various contexts, such as wound healing and tissue regeneration, PDGF-BB orchestrates the proliferation of various cell types, including fibroblasts and smooth muscle cells, critical for tissue repair and angiogenesis (4). Additionally, PDGF-BB governs cell migration by promoting cytoskeletal changes and focal adhesion dynamics, facilitating cell motility during physiological processes like development and wound closure.
Angiogenesis and Vascular Remodeling
Angiogenesis, the formation of new blood vessels, is orchestrated by intricate signaling networks, where PDGF-BB plays a central role (5) . PDGF-BB stimulates the recruitment and proliferation of pericytes and smooth muscle cells, critical for stabilizing nascent blood vessels. The interplay between PDGF-BB and vascular endothelial growth factor (VEGF) signaling is evident in the fine-tuning of angiogenic processes. PDGF-BB's contribution to vascular remodeling extends beyond angiogenesis, as it promotes the maturation of blood vessels and the maintenance of vascular integrity.
Tissue Repair and Regeneration
In the context of tissue injury, PDGF-BB emerges as a key player in orchestrating the repair and regeneration process (6). Its ability to stimulate fibroblast proliferation and extracellular matrix (ECM) production contributes to wound closure and tissue reconstitution. The fibrotic response mediated by PDGF-BB is essential for reestablishing tissue architecture, yet dysregulation can lead to excessive scarring and fibrosis, contributing to pathological conditions.
Implications in Pathology
While PDGF-BB's roles in physiological processes are essential, dysregulation can contribute to pathological conditions (7). Excessive PDGF-BB signaling is implicated in fibrotic diseases, such as pulmonary fibrosis and liver fibrosis, highlighting its dual role in normal repair and pathological remodeling. Furthermore, the aberrant activation of PDGF-BB signaling pathways has been linked to various cancers, including glioblastoma and certain sarcomas (8). Understanding the intricate balance between physiological and pathological PDGF-BB signaling is crucial for developing targeted therapeutic interventions.
PDGF-BB in Therapeutic Interventions
The intricate signaling pathways governed by PDGF-BB have spurred significant interest in its potential therapeutic applications. The ability of PDGF-BB to stimulate cell proliferation and angiogenesis has led to its exploration in tissue engineering and regenerative medicine (9). Targeting PDGF-BB signaling holds promise in promoting wound healing and tissue repair, particularly in cases of chronic non-healing wounds (10). Furthermore, the dysregulation of PDGF-BB signaling in fibrotic diseases has prompted investigations into novel therapeutic strategies. Emerging studies focus on modulating PDGF-BB pathways to attenuate excessive fibrosis and restore tissue homeostasis (11). As researchers unravel the intricate roles of PDGF-BB in different pathologies, the development of selective and efficacious interventions may hold the key to addressing unmet medical needs across diverse clinical contexts.
Conclusion
Platelet-Derived Growth Factor-BB (PDGF-BB) serves as a versatile orchestrator in cellular physiology, regulating diverse processes such as proliferation, migration, angiogenesis, and tissue repair. Its interactions with PDGFRα and PDGFRβ trigger intricate signaling cascades that ultimately shape cellular behavior and tissue microenvironments. The multifaceted nature of PDGF-BB underscores its potential as a therapeutic target across a spectrum of disorders, from tissue regeneration to cancer treatment. To harness the full potential of PDGF-BB modulation, further research is warranted to unravel its intricate molecular mechanisms and contextual effects in different biological systems.
References
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