lncRNA-ES3/miR-34c-5p/BMF axis is involved in regulating high-glucose-induced calcification/senescence of VSMCs
lncRNA-ES3/miR-34c-5p/BMF axis is involved in regulating high-glucose-induced calcification/senescence of VSMCs
复制标题
lncRNA-ES3/miR-34c-5p/BMF轴参与调节高糖诱导的VSMC钙化/衰老
DOI：
10.18632/aging.101758
复制
发表时间：
2019-01-31
期刊：
影响因子：
5.2
通讯作者：
Liu, You-Shuo
中科院分区：
文献类型：
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作者：
Lin, Xiao;Zhan, Jun-Kun;Liu, You-Shuo
血管钙化/老化在糖尿病患者中较为常见，且与患者发病率和死亡率的上升相关。在高糖诱导的人主动脉血管平滑肌细胞（HA - VSMCs）钙化/衰老过程中，显著受到抑制的是miR - 34c - 5p，而非miR - 34c - 3p，矿化结节的形成以及衰老相关β - 半乳糖苷酶染色（SA - β - gal）阳性细胞的染色证实了这一点。过表达miR - 34c - 5p可缓解HA - VSMCs的钙化/衰老，而抑制miR - 34c - 5p则得到相反的结果。Bcl - 2修饰因子（BMF）是miR - 34c - 5p的一个功能性靶标，且参与了HA - VSMCs的钙化/衰老过程。此外，长链非编码RNA - ES3（lncRNA - ES3）作为miR - 34c - 5p的竞争性内源性RNA（ceRNA），可增强BMF的表达。进一步研究发现，lncRNA - ES3通过直接相互作用抑制miR - 34c - 5p的表达，其表达下调可抑制HA - VSMCs的钙化/衰老。我们的研究结果首次表明，血管平滑肌细胞的钙化/衰老受lncRNA - ES3/miR - 34c - 5p/BMF轴调控。
Vascular calcification/aging is common in diabetes and is associated with increased morbidity and mortality of patients. MiR-34c-5p, not miR-34c-3p, was suppressed significantly in calcification/senescence of human aorta vascular smooth muscle cells (HA-VSMCs) induced by high glucose, which was proven by the formation of mineralized nodules and staining of senescence associated-β-galactosidase staining (SA β-gal) positive cells. Overexpression of miR-34c-5p alleviated calcification/senescence of HA-VSMCs, whereas inhibition of miR-34c-5p received the opposite results. Bcl-2 modifying factor (BMF) was a functional target of miR-34c-5p and it was involved in the process of calcification/senescence of HA-VSMCs. Besides, lncRNA-ES3 acted as a competing endogenous RNAs (ceRNA) of miR-34c-5p to enhance BMF expression. Further, lncRNA-ES3 inhibited miR-34c-5p expression by direct interaction and its knockdown suppressed the calcification/senescence of HA-VSMCs. Our results showed for the first time that the calcification/senescence of VSMCs was regulated by lncRNA-ES3 /miR-34c-5p/BMF axis.