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基质细胞衍生因子-1 促进氧化型低密度脂蛋白诱导的血管平滑肌细胞增殖。

SDF-1 promotes ox-LDL induced vascular smooth muscle cell proliferation.

机构信息

The First Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Cell Biol Int. 2013 Sep;37(9):988-94. doi: 10.1002/cbin.10126. Epub 2013 May 30.

Abstract

The mechanism of the regulatory roles of stromal cell derived factor-1 (SDF-1)/C-X-C motif receptor 4 (CXCR4) on cell proliferation and apoptosis in vascular smooth muscle cells (VSMCs) via the protein kinase C (PKC) and nuclear factor-kappa B (NF-κB) signalling pathways have been investigated. Rat aortic VSMCs were treated with control or an oxidised low-density lipoprotein (ox-LDL) atherosclerosis (AS) model. Cells exposed to the AS model were treated with SDF-1 plus inhibitors specific for PKC (Ro31-8220), CXCR4 (12G5) or NF-κB (pyrrolidine dithiocarbamate, PDTC). Cell proliferation was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis by flow cytometry. NF-κB protein expression was analysed using Western blotting. The proliferation rate in the AS model group was significantly higher than the control group, but lower than the SDF-1 group (P < 0.05). Apoptosis in the AS model group (ox-LDL) was significantly higher than the normal control group (P < 0.05). In addition, the apoptosis rate in the SDF-1 group was significantly lower than the normal control group (P < 0.05); however, there was no difference from the Ro31-8220 group. NF-κB protein expression in the SDF-1 group was significantly higher than the AS model (ox-LDL) group (P < 0.05). In conclusion, SDF-1 can promote the proliferation of VSMCs induced by ox-LDL and inhibit cell apoptosis, via the SDF-1/CXCR4 axis.

摘要

基质细胞衍生因子-1(SDF-1)/C-X-C 基序趋化因子受体 4(CXCR4)通过蛋白激酶 C(PKC)和核因子-κB(NF-κB)信号通路对血管平滑肌细胞(VSMCs)增殖和凋亡的调节作用机制已被研究。将大鼠主动脉 VSMCs 用对照或氧化型低密度脂蛋白(ox-LDL)动脉粥样硬化(AS)模型处理。将暴露于 AS 模型的细胞用 SDF-1 加 PKC(Ro31-8220)、CXCR4(12G5)或 NF-κB(吡咯烷二硫代氨基甲酸盐,PDTC)的抑制剂处理。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)测定法测量细胞增殖,通过流式细胞术测量细胞凋亡。用 Western 印迹分析 NF-κB 蛋白表达。AS 模型组的增殖率明显高于对照组,但低于 SDF-1 组(P<0.05)。AS 模型组(ox-LDL)的凋亡率明显高于正常对照组(P<0.05)。此外,SDF-1 组的凋亡率明显低于正常对照组(P<0.05);然而,与 Ro31-8220 组没有差异。SDF-1 组 NF-κB 蛋白表达明显高于 AS 模型(ox-LDL)组(P<0.05)。总之,SDF-1 可以通过 SDF-1/CXCR4 轴促进 ox-LDL 诱导的 VSMCs 增殖并抑制细胞凋亡。

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