PDF(Pubmed)
Abstract：
BACKGROUND: This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-β1 stimulated hepatic stellate cells (HSC-MVs, TGF-β1HSC-MVs) on H2O2-induced human umbilical vein endothelial cells (HUVECs) injury and CCl4-induced rat hepatic vascular injury.
METHODS: HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-β1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-β1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected.
RESULTS: In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-β1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-β1HSC-MVs demonstrated opposite effects.
CONCLUSIONS: HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-β1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.
METHODS: HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-β1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-β1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected.
RESULTS: In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-β1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-β1HSC-MVs demonstrated opposite effects.
CONCLUSIONS: HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-β1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.
摘要：
背景：这项研究评估了来自静止和TGF-β1刺激的肝星状细胞（HSC-MVs，TGF-β1HSC-MVs）对H2O2诱导的人脐静脉内皮细胞（HUVECs）损伤和CCl4诱导的大鼠肝血管损伤。
方法：HUVECs暴露于过氧化氢（H2O2）以建立血管内皮细胞损伤模型。HSC-MVs或TGF-β1HSC-MVs与H2O2处理的HUVECs共培养,分别。指标包括细胞存活率，凋亡率，氧化应激，迁移,入侵,测量血管生成。同时,PI3K等蛋白质的表达，AKT,MEK1+MEK2,ERK1+ERK2,VEGF,eNOS,并对CXCR4进行了评估，以及活化的caspase-3。SD大鼠腹腔注射CCl4,每周2次,连续10周,建立肝损伤模型。将HSC-MV或TGF-β1HSC-MV注射到大鼠的尾静脉中。还检测到肝和肝血管损伤。
结果：在H2O2处理的HUVECs中，HSC-MV增加细胞活力，降低细胞毒性和细胞凋亡，改善氧化应激，迁移,和血管生成，并上调PI3K的蛋白表达，AKT,MEK1/2、ERK1/2、VEGF、eNOS,和CXCR4。相反，TGF-β1HSC-MV表现出相反的作用。CCl4-诱导大鼠肝损伤模型,HSC-MV减少ALT和AST的释放，肝脏炎症,脂肪变形，和肝纤维化。HSC-MV还下调CD31和CD34的蛋白表达。相反，TGF-β1HSC-MV表现出相反的作用。
结论：HSC-MV对H2O2处理的HUVECs和CCl4诱导的大鼠肝损伤具有保护作用，而TGF-β1HSC-MVs有加重效应。MV的作用涉及PI3K/AKT/VEGF，CXCR4和MEK/ERK/eNOS通路。
方法：HUVECs暴露于过氧化氢（H2O2）以建立血管内皮细胞损伤模型。HSC-MVs或TGF-β1HSC-MVs与H2O2处理的HUVECs共培养,分别。指标包括细胞存活率，凋亡率，氧化应激，迁移,入侵,测量血管生成。同时,PI3K等蛋白质的表达，AKT,MEK1+MEK2,ERK1+ERK2,VEGF,eNOS,并对CXCR4进行了评估，以及活化的caspase-3。SD大鼠腹腔注射CCl4,每周2次,连续10周,建立肝损伤模型。将HSC-MV或TGF-β1HSC-MV注射到大鼠的尾静脉中。还检测到肝和肝血管损伤。
结果：在H2O2处理的HUVECs中，HSC-MV增加细胞活力，降低细胞毒性和细胞凋亡，改善氧化应激，迁移,和血管生成，并上调PI3K的蛋白表达，AKT,MEK1/2、ERK1/2、VEGF、eNOS,和CXCR4。相反，TGF-β1HSC-MV表现出相反的作用。CCl4-诱导大鼠肝损伤模型,HSC-MV减少ALT和AST的释放，肝脏炎症,脂肪变形，和肝纤维化。HSC-MV还下调CD31和CD34的蛋白表达。相反，TGF-β1HSC-MV表现出相反的作用。
结论：HSC-MV对H2O2处理的HUVECs和CCl4诱导的大鼠肝损伤具有保护作用，而TGF-β1HSC-MVs有加重效应。MV的作用涉及PI3K/AKT/VEGF，CXCR4和MEK/ERK/eNOS通路。
