Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs. I. The PI3K/AKT pathway and induction of phosphorylation of BAD
Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs. I. The PI3K/AKT pathway and induction of phosphorylation of BAD
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DOI：
10.1667/rr3158
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发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Deng, H
中科院分区：
文献类型：
--
作者：
Gu, QY;Wang, DW;Deng, H
辐射诱导的内皮细胞凋亡参与许多辐射损伤的发生，包括辐射诱导的皮肤溃疡。促血管生成生长因子碱性成纤维细胞生长因子（bFGF，NUDT 6）和VEGF增强内皮细胞存活。本研究以原代培养的人脐静脉内皮细胞（HU-VECs）为研究对象，探讨bFGF对辐射诱导HUVECs凋亡的影响及其信号通路。我们发现，bFGF抑制辐射诱导的HUVECs凋亡，这种作用是通过PI 3 K/AKT途径介导的。该途径通过将照射的HUVECs暴露于bFGF来激活，涉及FGFR、PI 3 K和AKT的磷酸化。wortmannin和LY 294002可阻断bFGF的促细胞存活作用。AKT显性负突变体的转染完全阻断了bFGF在辐射HUVECs中的抗凋亡作用。我们还首次发现了bFGF在照射后的HUVEC中诱导BAD磷酸化的证据。这些结果表明，PI 3 K/AKT通路参与了bFGF诱导的受辐射HUVECs存活的调节。PI 3 K/AKT通路的激活在bFGF诱导的内皮细胞存活中起重要作用，在治疗辐射诱导的皮肤溃疡中。(C)2004年，辐射研究协会。
Radiation-induced endothelial cell apoptosis is involved in the development of many radiation injuries, including radiation-induced skin ulcers. The proangiogenic growth factors basic fibroblast growth factor (bFGF, NUDT6) and VEGF enhance endothelial cell survival. In the present study, we used primary cultured human umbilical vein endothelial cells (HU-VECs) irradiated with Co-60 gamma rays to explore the effects of bFGF on radiation-induced apoptosis of HUVECs and its signaling pathways. We found that bFGF inhibited radiation-induced apoptosis of HUVECs, and that the effect was mediated by the PI3K/AKT pathway. This pathway was activated by exposure of irradiated HUVECs to bFGF, involving phosphorylation of FGFR, PI3K and AKT. The survival-enhancing effect of bFGF was abrogated by wortmannin and LY294002. Transfection of a dominant-negative mutant of AKT completely blocked the anti-apoptosis effect of bFGF in irradiated HUVECs. We also found evidence for the first time that bFGF induced BAD phosphorylation in they-irradiated HUVECs. These results showed that the PI3K/AKT pathway participated in the bFGF-induced modulation of the survival of irradiated HUVECs. Activation of the PI3K/AKT pathway plays an important role in bFGF-induced endothelial cell survival in the treatment of radiation-induced skin ulcers. (C) 2004 by Radiation Research Society.