Zhang Li, Yu Yang, Xia Xi, Ma Yang, Chen Xie-Wan, Ni Zhen-Hong, Wang Hong
Department of Postgraduate, Third Military Medical University, Chongqing 400038, P.R. China.
Department of Cardiology, Institute of Cardiovascular Science of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Int J Mol Med. 2016 May;37(5):1254-62. doi: 10.3892/ijmm.2016.2521. Epub 2016 Mar 9.
Endothelial progenitor cells (EPCs) play a key role in repairing the injured vascular endothelium by differentiating into mature endothelial cells (ECs) or secreting cytokines in a paracrine manner to promote proliferation of existing ECs. However, the mechanisms underlying the proliferation of EPCs were not fully understood. In order to investigate the mechanisms of EPC proliferation, we isolated EPCs from mononuclear cells of mouse spleens. By manipulating E2-2 expression in vitro, we observed that E2-2 negatively regulated the proliferation of EPCs. Moreover, we noted that E2-2 negatively regulated the autophagy of EPCs by studying the expression of LC3II and p62. We also demonstrated that an autophagy inhibitor chloroquine (CQ) decreased the proliferation of EPCs in a concentration-dependent manner. Interestingly, CQ reversed the increase in cell proliferation and autophagy in the E2-2 knockdown group. Furthermore, we detected the expression of autophagy‑related protein ATG7 in EPCs which had been transfected with small interfering (siRNA)‑E2-2 and siRNA‑autophagy related 7 (ATG7) or were untransfected. Our study revealed that E2-2 regulated EPC autophagy via mediating ATG7 expression. We conclude that E2-2 inhibited EPC proliferation via suppressing their autophagy, and E2-2 regulated EPC autophagy by mediating the expression of ATG7.
内皮祖细胞（EPCs）通过分化为成熟内皮细胞（ECs）或以旁分泌方式分泌细胞因子以促进现有ECs的增殖，在修复受损血管内皮中发挥关键作用。然而，EPCs增殖的潜在机制尚未完全明确。为了研究EPCs增殖的机制，我们从小鼠脾脏的单核细胞中分离出EPCs。通过在体外操纵E2-2的表达，我们观察到E2-2负向调节EPCs的增殖。此外，通过研究LC3II和p62的表达，我们注意到E2-2负向调节EPCs的自噬。我们还证明，自噬抑制剂氯喹（CQ）以浓度依赖的方式降低EPCs的增殖。有趣的是，CQ逆转了E2-2基因敲低组中细胞增殖和自噬的增加。此外，我们检测了用小干扰RNA（siRNA）-E2-2和siRNA-自噬相关蛋白7（ATG7）转染或未转染的EPCs中自噬相关蛋白ATG7的表达。我们的研究表明，E2-2通过介导ATG7的表达来调节EPCs的自噬。我们得出结论，E2-2通过抑制EPCs的自噬来抑制其增殖，并且E2-2通过介导ATG7的表达来调节EPCs的自噬。
