目的:探究双特异性磷酸酶6(Dusp6)对间歇性缺氧(IH)诱导的肺动脉高压(PAH)的影响及其机制。方法:利用基因表达数据库以及体内模型分析Dusp6的差异表达。随后将15只雄性SD大鼠随机分为正常组(Normal组)、慢性间歇缺氧组(CIH组,120 s循环,...目的:探究双特异性磷酸酶6(Dusp6)对间歇性缺氧(IH)诱导的肺动脉高压(PAH)的影响及其机制。方法:利用基因表达数据库以及体内模型分析Dusp6的差异表达。随后将15只雄性SD大鼠随机分为正常组(Normal组)、慢性间歇缺氧组(CIH组,120 s循环,60 s 6%O_(2),60 s 21%O_(2),8 h/d,持续6周)、CIH+Dusp6抑制组(CIH+AAV1. Dusp6组),CIH处理6周后观察各组大鼠右心收缩压以及肺外周小动脉重塑程度。同时,将大鼠肺动脉平滑肌细胞(RPASMCs)分为正常组、间歇缺氧组(IH组,1 h循环,30 min 1%O_(2),30 min 21%O_(2),持续24 h)、间歇缺氧+Dusp6抑制组(IH+Si-Dusp6组),观察各组RPASMCs增殖、线粒体膜电位和线粒体分裂情况。结果:基因表达数据库以及体内模型显示,与正常组相比,IH组Dusp6表达升高。与正常组相比,CIH组大鼠右心收缩压升高,肺外周小动脉明显重塑;而与CIH组相比,CIH+AAV1. Dusp6组大鼠右心收缩压有所下降,肺外周小动脉重塑程度明显减轻。同时,IH能够诱导RPASMCs的增殖、线粒体膜电位降低和线粒体分裂,而抑制Dusp6能够明显减轻IH诱导的RPASMCs增殖、线粒体膜电位的降低和线粒体分裂。另外,Dusp6能够通过调节Drp1/ERK1/2通路而发挥作用。结论:抑制Dusp6表达可能通过Drp1/ERK1/2通路调节线粒体分裂从而抑制CIH诱导的大鼠肺动脉高压。展开更多
Background The MAPK phosphatases （MKPs） are a family of dual-specificity phosphatases （DUSPs） that can dephosphorylate both phosphothreonine and phosphotyrosine residues,thus inactivating MAPK signaling.DUSP6 is a...Background The MAPK phosphatases （MKPs） are a family of dual-specificity phosphatases （DUSPs） that can dephosphorylate both phosphothreonine and phosphotyrosine residues,thus inactivating MAPK signaling.DUSP6 is a cytoplasmic MKP that can inactivate ERK.DUSP6 has been implicated in the development of some tumors.The aim of this research was to investigate the expression of DUSP6 in hepatocellular carcinoma （HCC） and the correlation of DUSP6 with mitogen-activated protein kinases （MAPKs）,clinicopathological characteristics,and prognosis.Methods Tissues from 305 patients who had undergone hepatectomy for HCC was used in this study.The expression of DUSP6,p-ERK,p-JNK,and p-p38a was determined using tissue microarrays for immunohistochemical analysis.The prognostic value of DUSP6 and other clinicopathological factors were evaluated.Results The expression of DUSP6 was significantly higher in the tumor tissue when compared to the peritumor or normal liver tissue （P ＜0.001）.Tumor DUSP6 expression was significantly associated with disease-free survival （DFS） （P=0.013）.Tumor DUSP6 expression was an independent prognostic factor for DFS （Hazard ratio =1.635,P=0.006）.Conclusions DUSP6 is over expressed in tumor tissue compared to peritumor or normal liver tissue.Higher expression of DUSP6 in tumor tissue,than in peritumor tissue,is associated with the recurrence after curative resection of HCC,and the relative tumor DUSP6 expression has good power to predict the recurrence of HCC.展开更多
文摘目的:探究双特异性磷酸酶6(Dusp6)对间歇性缺氧(IH)诱导的肺动脉高压(PAH)的影响及其机制。方法:利用基因表达数据库以及体内模型分析Dusp6的差异表达。随后将15只雄性SD大鼠随机分为正常组(Normal组)、慢性间歇缺氧组(CIH组,120 s循环,60 s 6%O_(2),60 s 21%O_(2),8 h/d,持续6周)、CIH+Dusp6抑制组(CIH+AAV1. Dusp6组),CIH处理6周后观察各组大鼠右心收缩压以及肺外周小动脉重塑程度。同时,将大鼠肺动脉平滑肌细胞(RPASMCs)分为正常组、间歇缺氧组(IH组,1 h循环,30 min 1%O_(2),30 min 21%O_(2),持续24 h)、间歇缺氧+Dusp6抑制组(IH+Si-Dusp6组),观察各组RPASMCs增殖、线粒体膜电位和线粒体分裂情况。结果:基因表达数据库以及体内模型显示,与正常组相比,IH组Dusp6表达升高。与正常组相比,CIH组大鼠右心收缩压升高,肺外周小动脉明显重塑;而与CIH组相比,CIH+AAV1. Dusp6组大鼠右心收缩压有所下降,肺外周小动脉重塑程度明显减轻。同时,IH能够诱导RPASMCs的增殖、线粒体膜电位降低和线粒体分裂,而抑制Dusp6能够明显减轻IH诱导的RPASMCs增殖、线粒体膜电位的降低和线粒体分裂。另外,Dusp6能够通过调节Drp1/ERK1/2通路而发挥作用。结论:抑制Dusp6表达可能通过Drp1/ERK1/2通路调节线粒体分裂从而抑制CIH诱导的大鼠肺动脉高压。
文摘Background The MAPK phosphatases （MKPs） are a family of dual-specificity phosphatases （DUSPs） that can dephosphorylate both phosphothreonine and phosphotyrosine residues,thus inactivating MAPK signaling.DUSP6 is a cytoplasmic MKP that can inactivate ERK.DUSP6 has been implicated in the development of some tumors.The aim of this research was to investigate the expression of DUSP6 in hepatocellular carcinoma （HCC） and the correlation of DUSP6 with mitogen-activated protein kinases （MAPKs）,clinicopathological characteristics,and prognosis.Methods Tissues from 305 patients who had undergone hepatectomy for HCC was used in this study.The expression of DUSP6,p-ERK,p-JNK,and p-p38a was determined using tissue microarrays for immunohistochemical analysis.The prognostic value of DUSP6 and other clinicopathological factors were evaluated.Results The expression of DUSP6 was significantly higher in the tumor tissue when compared to the peritumor or normal liver tissue （P ＜0.001）.Tumor DUSP6 expression was significantly associated with disease-free survival （DFS） （P=0.013）.Tumor DUSP6 expression was an independent prognostic factor for DFS （Hazard ratio =1.635,P=0.006）.Conclusions DUSP6 is over expressed in tumor tissue compared to peritumor or normal liver tissue.Higher expression of DUSP6 in tumor tissue,than in peritumor tissue,is associated with the recurrence after curative resection of HCC,and the relative tumor DUSP6 expression has good power to predict the recurrence of HCC.
