红细胞生成素3‘端增强子在肺动脉平滑肌细胞代氧性增殖调控中的作用

用噻唑蓝比色法（ＭＴＴ法）、Ｈ＾３－胸腺嘧啶核苷（Ｈ＾３－ＴｄＲ）掺入法和流式细胞术,观察红细胞生成素（ＥＰＯ）３’端增强子片段对培养的猪肺动脉平滑肌细胞（ＰＡＳＭＣｓ）的内皮依赖性和非内皮依赖性低氧性增殖的影响。结果为：（１）低氧２４ｈ后ＰＡＳＭＣｓ明显增殖,转入野生型ＥＰＯ３’端增强子片段可被抑制,而转入突变型片段无此作用;（２）肺动脉内皮细胞（ＰＡＥＣｓ）低氧２４ｈ,其条件培养液有明显的促Ｐ

Effect of erythropoietin 3-enhancer on proliferation of pulmonary artery smooth muscle cells induced by hypoxia

The effects of erythropoietin (EPO)3 -enhancer on endothelium-dependent and endothelium-independent proliferation caused by hypoxia in cultured porcine pulmonary artery smooth muscle cells (PASMCs) were investigated with MTT test, H(3)-TdR incorporation and flow-cytometry. The results showed that (1) PASMCs exposed to hypoxia for 24 h proliferated significantly, which was suppressed by pretransfecting wild type EPO3 -enhancer fragments into PASMCs, but not by protransfecting mutant fragments; and (2) the conditioned medium of pulmonary artery endothelial cells (PAECs) exposed to hypoxia for 24 h promoted the proliferation of PASMCs. This effect was abolished when wild type EPO3 -enhancer fragments were transfected, but it persisted when mutant fragments were transfected. The results suggest that (1) the conditioned medium of hypoxic PAECs induces proliferation of PASMCs. This may be because that not only PAECs are sensitive to hypoxia, but also PASMCs respond to hypoxia directly; and the hypoxic responses of both endothelial cells (ECs) and smooth muscle cells (SMCs) can be inhibited by exogenous EPO3 -enhancer fragments. (2) Since there is a HIF-1 binding site in EPO3 -enhancer, there may be a common pathway for HIF-1 hypoxia signal transduction in hypoxic responses of ECs and SMCs.