Key Laboratory of Nutrition and Metabolism, The Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
IUBMB Life. 2011 Jan;63(1):62-9. doi: 10.1002/iub.416.
Activating transcription factor 3 (ATF3) is a member of the ATF/CREB (CAMP responsive element binding protein) family of transcription factors. The expression and the function of ATF3 in vascular smooth muscle cells (VSMCs) remain unknown. The aim of this work is to determine the expression and possible function of ATF3 in VSMCs. We found that VSMCs expressed ATF3, and expression of ATF3 in VSMCs was induced by a variety of stimuli including serum, angiotensin II, and H(2)O(2). Knockdown of ATF3 induced apoptosis of VSMCs, caspase-3 cleavage, and cytochrome c release. The results suggest that ATF3 regulates survivability of VSMCs. Moreover, we found that overexpression of ATF3 promoted migration of VSMCs and induced expression of matrix metalloproteinase 1, 3, and 13. These results suggest that ATF3 plays a role in regulating migration of VSMCs. In addition, we found that the expression of ATF3 was upregulated in smooth muscle cells in the injured mouse femoral arteries compared with the uninjured control group. These results suggest that ATF3 is relevant to disease physiology.
激活转录因子 3(ATF3)是 ATF/CREB(CAMP 反应元件结合蛋白)家族转录因子的一员。ATF3 在血管平滑肌细胞(VSMCs)中的表达和功能尚不清楚。本研究旨在确定 ATF3 在 VSMCs 中的表达和可能的功能。我们发现 VSMCs 表达 ATF3,ATF3 的表达可被多种刺激诱导,包括血清、血管紧张素 II 和 H₂O₂。ATF3 的敲低诱导 VSMCs 凋亡、caspase-3 切割和细胞色素 c 释放。结果表明 ATF3 调节 VSMCs 的存活能力。此外,我们发现 ATF3 的过表达促进 VSMCs 的迁移,并诱导基质金属蛋白酶 1、3 和 13 的表达。这些结果表明 ATF3 在调节 VSMCs 的迁移中起作用。此外,我们发现与未损伤对照组相比,损伤小鼠股动脉中的平滑肌细胞中 ATF3 的表达上调。这些结果表明 ATF3 与疾病生理学相关。