TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells
TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells
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DOI：
10.1007/s00018-004-4197-6
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发表时间：
2004-07-01
影响因子：
8
通讯作者：
Zauli, G
中科院分区：
文献类型：
--
作者：
Secchiero, P;Zerbinati, C;Zauli, G
人和大鼠原代继代培养血管平滑肌细胞（VSMCs）均表达死亡受体TRAIL-R1和TRAIL-R2；然而，将重组可溶性TRAIL添加到这些细胞中不会诱导细胞死亡。TRAIL对炎性细胞因子肿瘤坏死因子- α +白细胞介素-1 - β +干扰素- γ或长时间血清停药诱导的大鼠VSMC凋亡均有保护作用，并显著促进VSMC增殖和迁移。值得注意的是，TRAIL诱导的所有生物学效应都被ERK通路的药理学抑制剂显著抑制。Western blot分析一致显示，TRAIL诱导ERK1/2显著活化，Akt磷酸化明显减弱，但不影响p38/MAPK通路。综上所述，这些数据加强了TRAIL/TRAIL- r系统可能通过影响VSMCs的存活、迁移和增殖在血管系统生物学中发挥作用的观点。
Human and rat primary sub-cultured vascular smooth muscle cells (VSMCs) showed clear expression of the death receptors TRAIL-R1 and TRAIL-R2; however, recombinant soluble TRAIL did not induce cell death when added to these cells. TRAIL tended to protect rat VSMCs from apoptosis induced either by inflammatory cytokines tumor necrosis factor-alpha + interleukin-1beta + interferon-gamma or by prolonged serum withdrawal, and promoted a significant increase in VSMC proliferation and migration. Of note, all the biological effects induced by TRAIL were significantly inhibited by pharmacological inhibitors of the ERK pathway. Western blot analysis consistently showed that TRAIL induced a significant activation of ERK1/2, and a much weaker phosphorylation of Akt, while it did not affect the p38/MAPK pathway. Taken together, these data strengthen the notion that the TRAIL/TRAIL-R system likely plays a role in the biology of the vascular system by affecting the survival, migration and proliferation of VSMCs.