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1 June 2004 Basic Fibroblast Growth Factor Inhibits Radiation-Induced Apoptosis of HUVECs. I. The PI3K/AKT Pathway and Induction of Phosphorylation of BAD
Qingyang Gu, Dewen Wang, Xiaodan Wang, Ruiyun Peng, Jie Liu, Tao Jiang, Zhaohai Wang, Shuiming Wang, Hua Deng
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Abstract

Gu, Q., Wang, D., Wang, X., Peng, R., Liu, J., Jiang, T., Wang, Z., Wang, S. and Deng, H. Basic Fibroblast Growth Factor Inhibits Radiation-Induced Apoptosis of HUVECs. I. The PI3K/AKT Pathway and Induction of Phosphorylation of BAD. Radiat. Res. 161, 692–702 (2004).

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 (HUVECs) irradiated with 60Co γ 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 the γ-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.

Qingyang Gu, Dewen Wang, Xiaodan Wang, Ruiyun Peng, Jie Liu, Tao Jiang, Zhaohai Wang, Shuiming Wang, and Hua Deng "Basic Fibroblast Growth Factor Inhibits Radiation-Induced Apoptosis of HUVECs. I. The PI3K/AKT Pathway and Induction of Phosphorylation of BAD," Radiation Research 161(6), 692-702, (1 June 2004). https://doi.org/10.1667/RR3158
Received: 21 February 2003; Accepted: 1 October 2003; Published: 1 June 2004
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