Kaempferol stimulates gene expression of low-density lipoprotein receptor through activation of Sp1 in cultured hepatocytes.
Kaempferol stimulates gene expression of low-density lipoprotein receptor through activation of Sp1 in cultured hepatocytes.
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DOI：
10.1038/srep24940
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发表时间：
2016-04-25
影响因子：
4.6
通讯作者：
Sato R
中科院分区：
文献类型：
--
作者：
Ochiai A;Miyata S;Iwase M;Shimizu M;Inoue J;Sato R
血浆低密度脂蛋白（LDL）胆固醇水平高被认为是动脉粥样硬化的危险因素。由于肝脏LDL受体（LDLR）是清除血浆LDL胆固醇所必需的，因此LDLR的激活是动脉粥样硬化疾病患者有希望的治疗靶点。在这里，我们证明了类黄酮山萘酚如何刺激HepG 2细胞中LDLR的基因表达和活性。山奈酚介导的LDLR基因表达的刺激被Sp1基因表达的敲低完全抑制。用山奈酚处理HepG 2细胞刺激了Sp1向LDLR基因启动子区的募集，以及Sp1在Thr-453和Thr-739上的磷酸化。此外，这些山奈酚介导的过程中，U 0126，ERK通路抑制剂的存在下被抑制。这些结果表明，山奈酚可能通过刺激ERK 1/2的Sp1磷酸化和随后诱导LDLR表达和活性来增加Sp1的活性。
A high level of plasma low-density lipoprotein (LDL) cholesterol is considered a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR) is essential for clearing plasma LDL cholesterol, activation of LDLR is a promising therapeutic target for patients with atherosclerotic disease. Here we demonstrated how the flavonoid kaempferol stimulated the gene expression and activity of LDLR in HepG2 cells. The kaempferol-mediated stimulation of LDLR gene expression was completely inhibited by knockdown of Sp1 gene expression. Treatment of HepG2 cells with kaempferol stimulated the recruitment of Sp1 to the promoter region of the LDLR gene, as well as the phosphorylation of Sp1 on Thr-453 and Thr-739. Moreover, these kaempferol-mediated processes were inhibited in the presence of U0126, an ERK pathway inhibitor. These results suggest that kaempferol may increase the activity of Sp1 through stimulation of Sp1 phosphorylation by ERK1/2 and subsequent induction of LDLR expression and activity.