目的:基于蛋白磷酸酶(PP1)-DNA依赖的蛋白激酶(DNA-PK)-上游刺激因子1(USF1)信号通路,探讨中药组分HJJB方防治非酒精性脂肪肝(NAFLD)的作用机制。方法:采用高脂饮食诱导的大鼠NAFLD模型。设模型组、HJJB方组和罗格列酮组,分别灌胃给药6...目的:基于蛋白磷酸酶(PP1)-DNA依赖的蛋白激酶(DNA-PK)-上游刺激因子1(USF1)信号通路,探讨中药组分HJJB方防治非酒精性脂肪肝(NAFLD)的作用机制。方法:采用高脂饮食诱导的大鼠NAFLD模型。设模型组、HJJB方组和罗格列酮组,分别灌胃给药6周。HE染色观察肝组织病理变化;测定肝组织甘油三酯(TG)、游离脂肪酸(FFA)含量的变化;肝组织PP1、DNA-PK、USF1 m RNA水平和蛋白含量的变化。结果:模型组肝组织出现显著的肝细胞脂肪变性及空泡样变,肝组织TG、FFA含量较正常组显著升高(P<0.01),肝组织PP1、DNA-PK、USF1 m RNA水平和蛋白含量较正常组均明显升高(P<0.01)。HJJB方组的上述病理改变明显减轻,肝组织TG、FFA含量较模型组显著降低(P<0.01),肝组织PP1、DNA-PK、USF1 m RNA水平和蛋白含量较模型组显著降低(P<0.01)。结论:HJJB方能显著降低脂肪肝大鼠肝组织PP1 m RNA水平和蛋白含量,进而抑制其下游信号通路,这可能是其防治NAFLD的重要机制。展开更多
This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma.We show that ERK5 expression is abun...This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma.We show that ERK5 expression is abundant in human lung cancer samples,and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential.Importantly,we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser910 site.Mechanistically,ERK5 increased the expression of the transcription factor USF1,which could transcriptionally upregulate FAK expression,resulting in FAK signaling activation to promote cell migration.We also provided evidence that the phosphorylation of FAK at Ser910 was due to ERK5 but not ERK1/2,and we then suggested a role for Ser910 in the control of cell motility.In addition,ERK5 had targets in addition to FAK that regulate epithelial-to-mesenchymal transition and cell motility in cancer cells.Taken together,our findings uncover a cancer metastasis-promoting role for ERK5 and provide the rationale for targeting ERK5 as a potential therapeutic approach.展开更多
文摘目的:基于蛋白磷酸酶(PP1)-DNA依赖的蛋白激酶(DNA-PK)-上游刺激因子1(USF1)信号通路,探讨中药组分HJJB方防治非酒精性脂肪肝(NAFLD)的作用机制。方法:采用高脂饮食诱导的大鼠NAFLD模型。设模型组、HJJB方组和罗格列酮组,分别灌胃给药6周。HE染色观察肝组织病理变化;测定肝组织甘油三酯(TG)、游离脂肪酸(FFA)含量的变化;肝组织PP1、DNA-PK、USF1 m RNA水平和蛋白含量的变化。结果:模型组肝组织出现显著的肝细胞脂肪变性及空泡样变,肝组织TG、FFA含量较正常组显著升高(P<0.01),肝组织PP1、DNA-PK、USF1 m RNA水平和蛋白含量较正常组均明显升高(P<0.01)。HJJB方组的上述病理改变明显减轻,肝组织TG、FFA含量较模型组显著降低(P<0.01),肝组织PP1、DNA-PK、USF1 m RNA水平和蛋白含量较模型组显著降低(P<0.01)。结论:HJJB方能显著降低脂肪肝大鼠肝组织PP1 m RNA水平和蛋白含量,进而抑制其下游信号通路,这可能是其防治NAFLD的重要机制。
基金This study was supported by grants from the Chinese National Natural Sciences Foundation(81773099,81570790)the National Key R&D Program of China(2017YFA0506000).
文摘This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma.We show that ERK5 expression is abundant in human lung cancer samples,and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential.Importantly,we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser910 site.Mechanistically,ERK5 increased the expression of the transcription factor USF1,which could transcriptionally upregulate FAK expression,resulting in FAK signaling activation to promote cell migration.We also provided evidence that the phosphorylation of FAK at Ser910 was due to ERK5 but not ERK1/2,and we then suggested a role for Ser910 in the control of cell motility.In addition,ERK5 had targets in addition to FAK that regulate epithelial-to-mesenchymal transition and cell motility in cancer cells.Taken together,our findings uncover a cancer metastasis-promoting role for ERK5 and provide the rationale for targeting ERK5 as a potential therapeutic approach.
