Liu Yong, Huang Junbin, Li Lindi, Duan Yifei, Chong Beng H, Li Liang, Yang Mo
Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.
Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.
Semin Thromb Hemost. 2025 Jun;51(5):572-577. doi: 10.1055/s-0044-1796630. Epub 2024 Nov 28.
Platelet-derived growth factor (PDGF) is a critical cytokine with substantial regulatory effects on hematopoiesis. Recent research highlights the essential role of PDGF in the modulation of hematopoietic stem/progenitor cells (HSPCs), megakaryocytes/platelets, and thrombopoietin (TPO) synthesis within the bone marrow microenvironment. PDGF directly stimulates the proliferation and differentiation of HSPCs while also inhibiting apoptosis. In addition, PDGF indirectly enhances the production of other growth factors, including granulocyte-macrophage colony-stimulating factors. Further, PDGF regulates TPO production and influences the bone marrow milieu, thus impacting hematopoiesis and platelet formation. Mechanistically, PDGF binds to its receptor, PDGF receptor (PDGFR), thus activating the PDGF/PDGFR signaling pathway. This pathway subsequently activates phosphoinositide 3-kinase/protein kinase B, leading to the activation of downstream cytokines, including c-Fos and NF-E2, while inhibiting caspase-3 activation. Collectively, these actions have prodifferentiation and antiapoptotic effects on megakaryocytes, thereby regulating platelet production. This review provides a comprehensive analysis of the regulatory role of the PDGF/PDGFR axis in hematopoiesis, with a particular focus on platelet production, by summarizing all studies on PDGF/PDGFR from our group and globally.
血小板衍生生长因子（PDGF）是一种对造血具有重要调节作用的关键细胞因子。最近的研究突出了PDGF在骨髓微环境中对造血干/祖细胞（HSPCs）、巨核细胞/血小板以及血小板生成素（TPO）合成的调节作用。PDGF直接刺激HSPCs的增殖和分化，同时抑制细胞凋亡。此外，PDGF间接增强包括粒细胞-巨噬细胞集落刺激因子在内的其他生长因子的产生。此外，PDGF调节TPO的产生并影响骨髓微环境，从而影响造血和血小板形成。从机制上讲，PDGF与其受体血小板衍生生长因子受体（PDGFR）结合，从而激活PDGF/PDGFR信号通路。该通路随后激活磷脂酰肌醇3-激酶/蛋白激酶B，导致包括c-Fos和NF-E2在内的下游细胞因子激活，同时抑制半胱天冬酶-3的激活。总体而言，这些作用对巨核细胞具有促分化和抗凋亡作用，从而调节血小板生成。本综述通过总结我们团队及全球范围内关于PDGF/PDGFR的所有研究，全面分析了PDGF/PDGFR轴在造血中的调节作用，尤其关注血小板生成。
