PDGFPDGFR对血小板生成的调节作用

文章编号（Article ID）：1009－2137（2011）05－1097－05·专论·PDGF/PDGFR对血小板生成的调节作用

杨默1，2，束玲玲1，崔韵1

1南方医科大学南方医院血液科，广东广州510515；2香港大学医学院药理学系，中国香港

摘要血小板衍生生长因子（PDGF）是重要的细胞因子，研究表明PDGF对造血干/祖细胞，巨核细胞/血小板、以及骨髓微环境的血小板生成素（TPO）合成都有重要的调节作用。PDGF可直接亦可通过促进其他生长因子生成如GM-CSF等促造血干/祖细胞的增殖和分化，抑制其凋亡。同时PDGF可调控TPO的生成及骨髓微环境，进而发挥对造血及血小板生成的调节作用，其机制可能为PDGF与血小板衍生生长因子受体（PDGFR）结合，启动PDGF/PDGFR信号通路，进而激活PI3K/Akt，促进相关细胞因子如C-Fos、NF-E2等的激活，抑制caspase-3的活化，从而发挥对巨核细胞的促分化和抗凋亡作用，进而调节血小板的生成。本文重点就PDGF/PDGFR对血小板生成的调节作用方面展开论述。

关键词血小板衍生生长因子；血小板衍生生长因子受体；造血干/祖细胞；巨核细胞；血小板；血小板生成素；PI3K/Akt信号通路

中图分类号R331．143文献标识码A

The Role of PDGF/PDGFR in the Regulation of Platelet Formation ———Editorial

YANG Mo1，2，SHU Ling-Ling1，CUI Yun1

1Department of Hematology，Sourthern Medical University Nanfang Hospital，Guangzhou510515，Guangdong Province，China；2Department of Pharmacology，LKS Faculty of Medicine，University of Hong Kong，Hong Kong，China

Corresponding Author：YANG Mo，Professor．Tel：（020）62787348．E-mail：yangm1091@yahoo．com．hk

Abstract Platelet-derived growth factor（PDGF），a potent chemotactic and mitogenic factor，is involved in the regulation of hematopoiesis and platelet production．Our studies demonstrate the presence of functional PDGF receptors （PDGFR）on human megakaryocytes/platelets and CD34+cells，and their ability to mediate a mitogenic response．PDGF promotes the ex vivo expansion of human hematopoietic stem（CD34+）and progenitor（CD41+）cells．More significantly，PDGF enhances the engraftment of human CD45+cells and their myeloid subsets（CD33+，CD14+cells）in NOD/SCID mice．PDGF also stimulates in vitro megakaryocytopoiesis via PDGFR and/or the indirect effect on bone marrow microenvironment to produce TPO and other cytokines．It also shows a direct stimulatory effect of PDGF on c-Fos，GATA-1and NF-E2expressions in megakaryocytes．We speculate that these transcription factors may be involved in the signal transduction of PDGF on the regulation of megakaryocytopoiesis．PDGF also enhances platelet recovery in mouse model with radiation-induced thrombocytopenia．This radioprotective effect is likely to be mediated via PDGFR with subsequent activation of the PI3K/Akt pathway．It provides a possible explanation that blockage of PDGFR may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia．

Key words PDGF；PDGFR；hematopoietic stem/progenitor cell；megakaryocytopoiesis；thrombocyte；TPO；PI3K/Akt pathway

J Exp Hematol2011；19（5）：1097－1101

血小板衍生生长因子（platelet-derived growth factor，PDGF）是一种重要的生长因子。在生理状态下，PDGF主要以α-蛋白颗粒（28－31kD）的形式储存于血小板中。它是由A、B、C和D4种肽链随机组合并以二硫键连接构成的二聚体，至少有AA、BB、CC、DD和AB5种亚型。PDGF受体（platelet-derived growth factor receptor，PDGFR）是一种跨膜糖蛋白，具有酪氨酸蛋白激酶活性。由细胞外N端与PDGF特异识别的结构域、单链顺序跨膜的中间疏水结构域和细胞内C端具有酪氨酸蛋白激酶活性的肽段结构域组成。PDGFR由α和β2种蛋白酪氨酸激酶亚基构成。研究发现，PDGF通过磷酸化激活PDGFR，启动PDGF/PDGFR信号通路来发挥其相应的生物学作用。PDGF/PDGFR的信号通路也被证实与一系列疾病的发生发展有关，

通讯作者：杨默，博士，教授．电话：（020）62787348．E-mail：yangm1091@yahoo．com．hk；yangmo@hku．hk

2011－06－09收稿；2011－06－21接受

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中国实验血液学杂志Journal of Experimental Hematology2011；19（5）：1097－1101