Dynamic interactions between cells and underlying extracellular matrices are crucial for development, maintenance of cellular function, and response of tissure to injury and infection. Heparan sulfate proteoglycans(HS...Dynamic interactions between cells and underlying extracellular matrices are crucial for development, maintenance of cellular function, and response of tissure to injury and infection. Heparan sulfate proteoglycans(HSPG)are found in extracellular matrices and on the surface of most nuclrarated cells, and play critical roles in cell-cell and cell-matrix signal transduction by binding many molecules, such as growth factors and cytokines. Most of the biological properties of HSPG are conferred by heparan sulfate side chains, which can be degraded by heparanase. Changes of heparanase expression and activity may affect the biological processes above, which enables extravasation of inflammation cells, metastasis and neoangiogenesis of tumor cells invasion.展开更多
目的探讨Toll样受体4(TLR4)信号通路在细胞外基质金属蛋白酶诱导因子(EMMPRIN)所介导的单核细胞白血病细胞株(THP-1)巨噬细胞调节基质金属蛋白酶(MMP)-9、MMP-14中的作用机制。方法实验分为对照组:THP-1巨噬细胞;刺激组:THP-1巨噬细胞+E...目的探讨Toll样受体4(TLR4)信号通路在细胞外基质金属蛋白酶诱导因子(EMMPRIN)所介导的单核细胞白血病细胞株(THP-1)巨噬细胞调节基质金属蛋白酶(MMP)-9、MMP-14中的作用机制。方法实验分为对照组:THP-1巨噬细胞;刺激组:THP-1巨噬细胞+EMMPRIN(1ng/ml)刺激6h;抑制组:THP-1巨噬细胞+TAK-242(5μmol/L)抑制4h,PBS清洗3次,再加EMMPRIN刺激6h。运用qRT-PCR和Western blot检测MMP-9、MMP-14基因;MMP-9、MMP-14和TLR4蛋白表达。结果光学显微镜下观察显示,THP-1单核细胞悬浮生长,呈圆形或类圆形,经100ng/ml佛波酯诱导分化48h,细胞体积增大,可伴有伪足伸出,呈椭圆形、长条梭形或短棒状,95%以上细胞贴壁生长。与对照组比较,刺激组MMP-9、MMP-14基因以及MMP-9、MMP-14和TLR4蛋白表达明显升高,抑制组TLR4蛋白表达明显下降,差异有统计学意义(P<0.05)。与刺激组比较,抑制组MMP-9、MMP-14基因以及MMP-9、MMP-14和TLR4蛋白表达明显下降(4.384±0.732 vs 6.473±0.739,3.178±0.492 vs 4.937±0.538,0.635±0.115 vs 0.832±0.114,0.454±0.067 vs 0.733±0.128,0.206±0.058 vs 0.481±0.086,P<0.05)。结论TLR4信号通路在EMMPRIN所介导的THP-1巨噬细胞上调MMP-9、MMP-14表达中起积极作用。展开更多
文摘Dynamic interactions between cells and underlying extracellular matrices are crucial for development, maintenance of cellular function, and response of tissure to injury and infection. Heparan sulfate proteoglycans(HSPG)are found in extracellular matrices and on the surface of most nuclrarated cells, and play critical roles in cell-cell and cell-matrix signal transduction by binding many molecules, such as growth factors and cytokines. Most of the biological properties of HSPG are conferred by heparan sulfate side chains, which can be degraded by heparanase. Changes of heparanase expression and activity may affect the biological processes above, which enables extravasation of inflammation cells, metastasis and neoangiogenesis of tumor cells invasion.
文摘目的探讨Toll样受体4(TLR4)信号通路在细胞外基质金属蛋白酶诱导因子(EMMPRIN)所介导的单核细胞白血病细胞株(THP-1)巨噬细胞调节基质金属蛋白酶(MMP)-9、MMP-14中的作用机制。方法实验分为对照组:THP-1巨噬细胞;刺激组:THP-1巨噬细胞+EMMPRIN(1ng/ml)刺激6h;抑制组:THP-1巨噬细胞+TAK-242(5μmol/L)抑制4h,PBS清洗3次,再加EMMPRIN刺激6h。运用qRT-PCR和Western blot检测MMP-9、MMP-14基因;MMP-9、MMP-14和TLR4蛋白表达。结果光学显微镜下观察显示,THP-1单核细胞悬浮生长,呈圆形或类圆形,经100ng/ml佛波酯诱导分化48h,细胞体积增大,可伴有伪足伸出,呈椭圆形、长条梭形或短棒状,95%以上细胞贴壁生长。与对照组比较,刺激组MMP-9、MMP-14基因以及MMP-9、MMP-14和TLR4蛋白表达明显升高,抑制组TLR4蛋白表达明显下降,差异有统计学意义(P<0.05)。与刺激组比较,抑制组MMP-9、MMP-14基因以及MMP-9、MMP-14和TLR4蛋白表达明显下降(4.384±0.732 vs 6.473±0.739,3.178±0.492 vs 4.937±0.538,0.635±0.115 vs 0.832±0.114,0.454±0.067 vs 0.733±0.128,0.206±0.058 vs 0.481±0.086,P<0.05)。结论TLR4信号通路在EMMPRIN所介导的THP-1巨噬细胞上调MMP-9、MMP-14表达中起积极作用。