Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway
Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway
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Visfatin 通过 PI3K/Akt/ERK 通路上调 SIRT1 表达，从而减轻 ox-LDL 诱导的内皮祖细胞衰老
DOI：
10.3892/ijmm.2016.2633
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发表时间：
2016-08-01
影响因子：
5.4
通讯作者：
Xiao, Jian
中科院分区：
文献类型：
--
作者：
Ming, Guang-Feng;Tang, Yong-Jun;Xiao, Jian
内皮祖细胞（EPC）在与衰老相关的衰老中发挥着重要作用，从而可能导致血管病变。 Visfatin被认为是一种新的脂肪细胞因子，与人体细胞的衰老密切相关。然而，据我们所知，内脂素对氧化低密度脂蛋白（ox-LDL）诱导的 EPC 衰老的影响尚未得到探索。为此，在本研究中，我们检查了内脂素对 ox-LDL 刺激的 EPC 的影响以及造成这些影响的潜在机制。我们发现内脂素通过抑制β半乳糖苷酶表达并恢复端粒酶活性来减轻ox-LDL诱导的EPC衰老。蛋白质印迹分析证实，visfatin 诱导 EPC 中 Sirtuin 1 (SIRT1) 表达呈剂量依赖性增加，ox-LDL 暴露可降低 SIRT1 表达。沉默 SIRT1 消除了内脂素诱导的 EPC 衰老抑制和 p53 表达抑制。此外，visfatin 减弱了 ox-LDL 诱导的 Akt、磷酸肌醇 3 激酶 (PI3K) 和细胞外信号调节激酶 (ERK) 磷酸化的抑制。总而言之，这些发现表明，用内脂素治疗 EPC 可以通过 PI3K/Akt/ERK 途径上调 SIRT1 表达，从而显着减轻 ox-LDL 诱导的 EPC 衰老。
Endothelial progenitor cells (EPCs) play an important role in aging-associated senescence, thereby potentially contributing to vascular pathologies. Visfatin, identified as a new adipocytokine, is closely associated with the senescence of human cells. However, the effects of visfatin on the oxidized low-density lipoprotein (ox-LDL)-induced senescence of EPCs has not yet been explored, to the best of our knowledge. For this purpose, in the present study, we examined the effects of visfatin in ox-LDL-stimulated EPCs as well as the underlying mechanism responsible for these effects. We found that visfatin attenuated the ox-LDL-induced senescence of EPCs by repressing -galactosidase expression and recovering telomerase activity. Western blot analysis confirmed that visfatin induced a dose-dependent increase in sirtuin 1 (SIRT1) expression in EPCs and ox-LDL exposure decreased SIRT1 expression. Silencing SIRT1 abolished the inhibition of EPC senescence and the suppression of p53 expression induced by visfatin. Moreover, visfatin attenuated the inhibition of phosphorylation of Akt, phosphoinositide-3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) induced by ox-LDL. Taken together, these findings suggest that the treatment of EPCs with visfatin markedly attenuates the ox-LDL-induced senescence of EPCs by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway.