Jung Sung-Cherl, Kang Dawon, Ko Eun-A
Department of Physiology, College of Medicine, Jeju National University, Jeju 63243, Korea.
Department of Physiology, College of Medicine and Institute of Medical Sciences, Gyeongsang National University, Jinju 52727, Korea.
Korean J Physiol Pharmacol. 2025 Mar 1;29(2):139-155. doi: 10.4196/kjpp.24.309. Epub 2024 Oct 31.
Platelet-derived growth factors (PDGFs) ligands and their corresponding receptors, PDGF receptor (PDGFR)α and PDGFRβ, play a crucial role in controlling diverse biological functions, including cell growth, viability and migration. These growth factors bind to PDGFRs, which are receptor tyrosine kinases present on the surface of target cells. The interaction between PDGFs and PDGFRs induces receptor dimerization and subsequent activation through auto-phosphorylation, which in turn triggers a cascade of intracellular signaling pathways. PDGF/PDGFR signaling is essential for maintaining normal physiological functions, including tissue regeneration and growth. However, dysregulation of this signaling pathway leads to pathological conditions, including fibrosis, atherosclerosis, and cancer development in various organs. The pathological impact of PDGF/PDGFR signaling primarily stems from its capacity to promote excessive cell proliferation, enhanced migration, and increased extracellular matrix deposition, resulting in tissue overgrowth, scarring, and abnormal vessel formation. These processes are integral to the pathogenesis of fibrotic, neoplastic, and vascular disorders. Therefore, understanding these pathways is crucial for developing targeted treatments designed to inhibit PDGF/PDGFR signaling in these diseases. This review delves into the dual role of PDGF/PDGFR signaling in both physiological and pathophysiological contexts across different organs and provides insights into current pharmacological therapies designed to target the PDGF signaling pathway.
血小板衍生生长因子（PDGFs）配体及其相应受体，即血小板衍生生长因子受体（PDGFR）α和PDGFRβ，在控制多种生物学功能中发挥着关键作用，这些功能包括细胞生长、活力和迁移。这些生长因子与PDGFRs结合，PDGFRs是存在于靶细胞表面的受体酪氨酸激酶。PDGFs与PDGFRs之间的相互作用诱导受体二聚化，并通过自身磷酸化随后激活，这进而触发一系列细胞内信号通路。PDGF/PDGFR信号传导对于维持正常生理功能至关重要，包括组织再生和生长。然而，该信号通路的失调会导致病理状况，包括纤维化、动脉粥样硬化以及各个器官的癌症发展。PDGF/PDGFR信号传导的病理影响主要源于其促进过度细胞增殖、增强迁移以及增加细胞外基质沉积的能力，从而导致组织过度生长、瘢痕形成和异常血管形成。这些过程是纤维化、肿瘤性和血管性疾病发病机制的组成部分。因此，了解这些信号通路对于开发旨在抑制这些疾病中PDGF/PDGFR信号传导的靶向治疗至关重要。本综述深入探讨了PDGF/PDGFR信号传导在不同器官的生理和病理生理背景下的双重作用，并提供了针对PDGF信号通路的当前药物治疗的见解。
