Potentiated activation of VLA-4 and VLA-5 accelerates proplatelet-like formation
Potentiated activation of VLA-4 and VLA-5 accelerates proplatelet-like formation
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DOI：
10.1007/s00277-012-1498-y
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发表时间：
2012-10-01
影响因子：
3.5
通讯作者：
Shimoda, Kazuya
中科院分区：
文献类型：
--
作者：
Matsunaga, Takuya;Fukai, Fumio;Shimoda, Kazuya
纤维连接蛋白（FN）通过其受体在巨核系细胞的增殖、分化和维持中起重要作用。然而，FN受体的实质性作用及其在巨核细胞前血小板样形成（PPF）中的功能分配尚未完全了解。在此，我们研究了FN受体对PPF的影响，使用CHRF-288人巨核细胞系，表达VLA-4和VLA-5作为FN受体。FN和佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）是诱导CHRF-288细胞PPF的必要条件。使用抗β 1-整合素单克隆抗体的阻断实验表明，PPF需要通过VLA-4和VLA-5与FN粘附相互作用。当CHRF-288细胞通过TNIIIA 2（一种来自生腱蛋白-C的肽，我们最近发现其诱导β 1-整合素活化）强制粘附于FN时，由FN加PMA诱导的PPF加速。粘附到FN增强PMA刺激的细胞外信号调节蛋白激酶1（ERK 1）/2的激活，并通过TNIIIA 2加速FN加PMA激活ERK 1/2，通过VLA-4和VLA-5增强粘附到FN。然而，c-Jun氨基末端激酶1（JNK 1），p38，和磷酸肌醇-3激酶（PI 3 K）/Akt不刺激FN加PMA，甚至与TNIIIA 2。因此，FN、PMA和TNIIIA 2对ERK 1/2的激活增强是FN和PMA促进PPF的原因。
Fibronectin (FN) plays important roles in the proliferation, differentiation, and maintenance of megakaryocytic-lineage cells through FN receptors. However, substantial role of FN receptors and their functional assignment in proplatelet-like formation (PPF) of megakaryocytes are not yet fully understood. Herein, we investigated the effects of FN receptors on PPF using the CHRF-288 human megakaryoblastic cell line, which expresses VLA-4 and VLA-5 as FN receptors. FN and phorbol 12-myristate 13-acetate (PMA) were essential for inducing PPF in CHRF-288 cells. Blocking experiments using anti-beta 1-integrin monoclonal antibodies indicated that the adhesive interaction with FN via VLA-4 and VLA-5 were required for PPF. PPF induced by FN plus PMA was accelerated when CHRF-288 cells were enforced adhering to FN by TNIIIA2, a peptide derived from tenascin-C, which we recently found to induce beta 1-integrin activation. Adhesion to FN enhanced PMA-stimulated activation of extracellular signal-regulated protein kinase 1 (ERK1)/2 and enforced adhesion to FN via VLA-4 and VLA-5 by TNIIIA2-accelerated activation of ERK1/2 with FN plus PMA. However, c-Jun amino-terminal kinase 1 (JNK1), p38, and phosphoinositide-3 kinase (PI3K)/Akt were not stimulated by FN plus PMA, even with TNIIIA2. Thus, the enhanced activation of ERK1/2 by FN, PMA plus TNIIIA2 was responsible for acceleration of PPF with FN plus PMA.