LncRNA AC096664.3/PPAR-gamma/ABCG1-dependent signal transduction pathway contributes to the regulation of cholesterol homeostasis
LncRNA AC096664.3/PPAR-gamma/ABCG1-dependent signal transduction pathway contributes to the regulation of cholesterol homeostasis
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LncRNA AC096664.3/PPAR-gamma/ABCG1依赖性信号转导途径有助于胆固醇稳态的调节
DOI：
10.1002/jcb.28650
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发表时间：
2019
影响因子：
4
通讯作者：
Wang Qian
中科院分区：
文献类型：
--
作者：
Xu Bang-Ming;Xiao Lei;Kang Chun-Min;Ding Li;Guo Feng-Xia;Li Pan;Lu Zhi-Feng;Wu Qian;Xu Yuan-Jun;Bai Huan-Lan;Tang Jun-Yi;Zheng Lei;Hu Yan-Wei;Wang Qian
动脉粥样硬化是一种复杂的炎症性疾病，涉及细胞胆固醇水平的破坏和泡沫细胞的形成。关于长链非编码RNA （lncRNA）的研究揭示了其在动脉粥样硬化发展中的作用，通过介导胆固醇的逆向转运和泡沫细胞的形成。在这项研究中，我们发现氧化低密度脂蛋白（ox‐LDL）显著降低血管平滑肌细胞（VSMCs）和THP‐1巨噬细胞中的lncRNA AC096664.3。我们还发现ox‐LDL通过抑制VSMCs中的lncRNA AC096664.3降低ATP结合盒（ABC） G1。进一步的实验表明，lncRNA AC096664.3的下调通过抑制过氧化物酶体增殖物激活受体γ （PPAR‐γ）的表达降低ABCG1的表达，ox‐LDL通过抑制PPAR‐γ的表达降低ABCG1的表达。此外，我们发现ox‐LDL通过lncRNA AC096664.3/PPAR‐γ/ABCG1途径抑制ABCG1，导致VMSCs中总胆固醇和游离胆固醇增加。因此，我们证实了ox‐LDL在VSMCs中通过lncRNA AC096664.3/PPAR‐γ/ABCG1途径诱导胆固醇积累，这表明了一种有希望的预防动脉粥样硬化的新疗法。
Atherosclerosis is a complex inflammatory disease that involves disrupted cellular cholesterol levels and formation of foam cells. Studies about long noncoding RNA (lncRNA) have revealed its function in the development of atherosclerosis, by mediating reverse cholesterol transport and formation of foam cells. In this study, we found that oxidized low‐density lipoprotein (ox‐LDL) markedly decreased lncRNA AC096664.3 in vascular smooth muscle cells (VSMCs) and THP‐1 macrophages. We also found that ox‐LDL reduced ATP‐binding cassette (ABC) G1 through inhibiting lncRNA AC096664.3 in VSMCs. Further experiments showed that the downregulation of lncRNA AC096664.3 reduced ABCG1 expression through inhibiting the expression of peroxisome proliferator–activated receptor‐γ (PPAR‐γ) and that ox‐LDL reduced ABCG1 expression through inhibiting the expression of PPAR‐γ. Furthermore, we discovered that ox‐LDL inhibited ABCG1 via the lncRNA AC096664.3/PPAR‐γ/ABCG1 pathway, which led to an increase in total and free cholesterol in VMSCs. Thus, we confirmed that ox‐LDL induces cholesterol accumulation via the lncRNA AC096664.3/PPAR‐γ/ABCG1 pathway in VSMCs, indicating a promising novel therapy in protecting against atherosclerosis.