Naringin inhibits matrix metalloproteinase-9 expression and AKT phosphorylation in tumor necrosis factor-α-induced vascular smooth muscle cells
Naringin inhibits matrix metalloproteinase-9 expression and AKT phosphorylation in tumor necrosis factor-α-induced vascular smooth muscle cells
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DOI：
10.1002/mnfr.200800210
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发表时间：
2009-12-01
影响因子：
5.2
通讯作者：
Moon, Sung-Kwon
中科院分区：
文献类型：
--
作者：
Lee, Eo-Jin;Kim, Dong-Il;Moon, Sung-Kwon
柑橘类水果富含柚皮苷，对心血管疾病有有益作用。然而，参与细胞迁移和侵袭的基质金属蛋白酶 9 (MMP-9) 调节仍有待确定。在10-25μM浓度条件下，柚皮苷抑制血管平滑肌细胞(VSMC)中肿瘤坏死因子-α(TNF-α)诱导的MMP-9表达。柚皮苷抑制TNF-α诱导的VSMC侵袭和迁移。此外，柚皮苷抑制 TNF-α 介导的白细胞介素 6 和 -8（IL-6 和 IL-8）的释放。然而，在TNF-α存在的情况下，柚皮苷(10-25μM)处理VSMC并不影响细胞生长和凋亡。在其他实验中，柚皮苷降低了激活蛋白 1 和核因子 kappaB (NF-kappa B) 的转录活性，这两个因子是参与 MMP-9 表达的重要核转录因子。此外，柚皮苷治疗阻断 TNF-α 诱导的 VSMC 中的 PI3K/AKT/mTOR/p70S6K 通路。与柚皮苷处理相比，苷元柚皮素(10-25μM)处理对TNF-α诱导的VSMC中MMP-9表达、侵袭、迁移和AKT磷酸化水平具有相同的影响。这些结果表明柚皮苷抑制 PI3K/AKT/mTOR/p70S6K 通路、侵袭和迁移，并随后通过 TNF-α 诱导的 VSMC 中的转录因子 NF-kappa B 和激活蛋白-1 抑制 MMP-9 的表达。这些新发现为柚皮苷预防动脉粥样硬化疾病提供了理论基础。
Citrus fruits are high in naringin, which has a beneficial effect on cardiovascular diseases. However, the matrix metalloproteinase-9 (MMP-9) regulation involved in cell migration and invasion remains to be identified. Naringin inhibited tumor necrosis factor-alpha (TNF-alpha)induced expression of MMP-9, under 10-25 mu M concentration conditions in vascular smooth muscle cells (VSMC). The TNF-alpha-induced invasion and migration of VSMC were inhibited by naringin. Furthermore, naringin suppressed TNF-alpha-mediated release of interleukin-6 and -8 (IL-6 and IL-8). However, naringin (10-25 mu M) treatment of VSMC in the presence of TNF-alpha did not affect cell growth and apoptosis. In additional experiments, naringin reduced the transcriptional activity of activator protein-1 and nuclear factor kappaB (NF-kappa B), which are two important nuclear transcription factors that;are involved in MMP-9 expression. Also, naringin treatment blocked PI3K/AKT/mTOR/p70S6K pathway in TNF-alpha-induced VSMC. Treatment of aglycone naringenin (10-25 mu M) had same effect on the levels of MMP-9 expression, invasion, migration, and AKT phosphorylation in TNF-alpha-induced VSMC, compared with naringin treatment. These results suggest that naringin represses PI3K/AKT/mTOR/p70S6K pathway, invasion and migration, and subsequently suppresses MMP-9 expression through the transcription factors NF-kappa B and activator protein-1 in TNF-alpha-induced VSMC. These novel findings provide a theoretical basis for the preventive use of naringin for atherosclerosis disease.