目的 研究固醇调节元件结合蛋白1（SREBP1）在血管紧张素II（Ang II）诱导的血管平滑肌细胞（VSMC）表型转化中的作用。方法 将C57BL/6J小鼠分为对照组、处理组1（150 ng/kg/min Ang II）、处理组2（300 ng/kg/min Ang II）、处理组3（6...目的 研究固醇调节元件结合蛋白1（SREBP1）在血管紧张素II（Ang II）诱导的血管平滑肌细胞（VSMC）表型转化中的作用。方法 将C57BL/6J小鼠分为对照组、处理组1（150 ng/kg/min Ang II）、处理组2（300 ng/kg/min Ang II）、处理组3（600 ng/kg/min Ang II）和缬沙坦组（600 ng/kg/min Ang II＋40 mg/kg/d 缬沙坦）处理28 d。观测小鼠血压和动脉血管变化。实时荧光定量PCR和免疫印迹检测血管SREBP1的表达。将VSMC分为正常组、处理组1 （0.1×10-6 mol/L Ang II）、处理组2（0.5×10-6 mol/L Ang II）、处理组3（1×10-6 mol/L Ang II）、缬沙坦组（1×10-6 mol/L Ang II＋1×10-6 mol/L 缬沙坦）、LY294002组（1×10-6 mol/L Ang II＋10 ng/mL LY294002）、沉默对照组（1×10-6 mol/L Ang II＋scramble siRNA）、沉默组（1×10-6 mol/L Ang II＋SREBP1 siRNA）处理，免疫印迹检测细胞SREBP1、Akt、磷酸化Akt（p-Akt）、α平滑肌肌动蛋白（α-SMA）、骨桥蛋白（OPN）的表达。 结果 与对照组比较，Ang II处理组小鼠收缩压和舒张压明显升高，缬沙坦组与处理组比较血压降低。相比于对照组，处理组小鼠血管壁增厚、管腔增大，缬沙坦处理则抑制血管重塑。Ang II处理组小鼠主动脉血管SREBP1 mRNA和蛋白表达水平高于对照组和缬沙坦组。SREBP1、磷酸化Akt、OPN在处理组VSMC细胞中表达水平高于正常组，而在缬沙坦组、LY294002组和沉默组中低于处理组；α-SMA在处理组中表达降低，而在缬沙坦组、LY294002组和沉默组中升高。 结论 Ang II通过活化PI3K/Akt/SREBP1通路调控VSMC表型转化、诱导小鼠动脉血管重塑。展开更多
Structural alterations in fibroelastic compone nts of the penile corpus caver no usum(CC)may impair its compliance,resulting in venous leakage and erectile dysfunction(ED).Our study evaluated the effectiveness of noni...Structural alterations in fibroelastic compone nts of the penile corpus caver no usum(CC)may impair its compliance,resulting in venous leakage and erectile dysfunction(ED).Our study evaluated the effectiveness of noninvasive two-dimensional shear-wave elastography(2-D SWE)in quantifying penile CC lesions in rabbits with hyperlipidemia-induced ED.A total of 12 New Zealand white rabbits were randomly divided into two groups.Six were fed a high-cholesterol diet containing 2%cholesterol and 8.5%lard for 10 weeks and the other six were fed normal diet as controls.We measured the shear-wave elastic quantitative(SWQ)value of penile CC by 2-D SWE.Erectile function was inv estigated by intracavernous injecti on of pa pa ver i ne,and immunohistochemical(IHC)stain inga nd the wester n blot analysis to determine the penile CC lesions.After 10 weeks,the SWQ values obtained from penile CC were remarkably higher in the high-cholesterol-fed compared with the control group,and the AICP(ICP plateau minus ICP baseline)/MAP(ICP:intracavernous pressure,MAP:mean arterial pressure)was markedly decreased.The IHC staining and western blot revealed extracellular matrix(ECM)accumulation in penile cavernous tissues,and the smooth muscle cell(SMC)phenotypic transition was affected,as indicated by reduced alpha-smooth muscle actin and calponinexpression and increased phospho-myosin light chain?。(p-MLC20)/MLC20 and osteopontin expression.Hyperlipidemia resulted in ECM accumulation accompanied with SMC phenotypic transition in penile CC and impaired the erectile function eventually.These might,in turn,lead to variations in the SWQ values.It suggests that 2-D SWE may be a novel,noninvasive and effective approach that distinguishes penile CC lesions secondary to hyperlipidemia from normal.展开更多
Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms we...Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.展开更多
文摘目的 研究固醇调节元件结合蛋白1（SREBP1）在血管紧张素II（Ang II）诱导的血管平滑肌细胞（VSMC）表型转化中的作用。方法 将C57BL/6J小鼠分为对照组、处理组1（150 ng/kg/min Ang II）、处理组2（300 ng/kg/min Ang II）、处理组3（600 ng/kg/min Ang II）和缬沙坦组（600 ng/kg/min Ang II＋40 mg/kg/d 缬沙坦）处理28 d。观测小鼠血压和动脉血管变化。实时荧光定量PCR和免疫印迹检测血管SREBP1的表达。将VSMC分为正常组、处理组1 （0.1×10-6 mol/L Ang II）、处理组2（0.5×10-6 mol/L Ang II）、处理组3（1×10-6 mol/L Ang II）、缬沙坦组（1×10-6 mol/L Ang II＋1×10-6 mol/L 缬沙坦）、LY294002组（1×10-6 mol/L Ang II＋10 ng/mL LY294002）、沉默对照组（1×10-6 mol/L Ang II＋scramble siRNA）、沉默组（1×10-6 mol/L Ang II＋SREBP1 siRNA）处理，免疫印迹检测细胞SREBP1、Akt、磷酸化Akt（p-Akt）、α平滑肌肌动蛋白（α-SMA）、骨桥蛋白（OPN）的表达。 结果 与对照组比较，Ang II处理组小鼠收缩压和舒张压明显升高，缬沙坦组与处理组比较血压降低。相比于对照组，处理组小鼠血管壁增厚、管腔增大，缬沙坦处理则抑制血管重塑。Ang II处理组小鼠主动脉血管SREBP1 mRNA和蛋白表达水平高于对照组和缬沙坦组。SREBP1、磷酸化Akt、OPN在处理组VSMC细胞中表达水平高于正常组，而在缬沙坦组、LY294002组和沉默组中低于处理组；α-SMA在处理组中表达降低，而在缬沙坦组、LY294002组和沉默组中升高。 结论 Ang II通过活化PI3K/Akt/SREBP1通路调控VSMC表型转化、诱导小鼠动脉血管重塑。
基金the National Natural Science Foundation of China(Grant No.81401195)Nature Science Foundation of Shanghai(Grant No.17ZR1422400).
文摘Structural alterations in fibroelastic compone nts of the penile corpus caver no usum(CC)may impair its compliance,resulting in venous leakage and erectile dysfunction(ED).Our study evaluated the effectiveness of noninvasive two-dimensional shear-wave elastography(2-D SWE)in quantifying penile CC lesions in rabbits with hyperlipidemia-induced ED.A total of 12 New Zealand white rabbits were randomly divided into two groups.Six were fed a high-cholesterol diet containing 2%cholesterol and 8.5%lard for 10 weeks and the other six were fed normal diet as controls.We measured the shear-wave elastic quantitative(SWQ)value of penile CC by 2-D SWE.Erectile function was inv estigated by intracavernous injecti on of pa pa ver i ne,and immunohistochemical(IHC)stain inga nd the wester n blot analysis to determine the penile CC lesions.After 10 weeks,the SWQ values obtained from penile CC were remarkably higher in the high-cholesterol-fed compared with the control group,and the AICP(ICP plateau minus ICP baseline)/MAP(ICP:intracavernous pressure,MAP:mean arterial pressure)was markedly decreased.The IHC staining and western blot revealed extracellular matrix(ECM)accumulation in penile cavernous tissues,and the smooth muscle cell(SMC)phenotypic transition was affected,as indicated by reduced alpha-smooth muscle actin and calponinexpression and increased phospho-myosin light chain?。(p-MLC20)/MLC20 and osteopontin expression.Hyperlipidemia resulted in ECM accumulation accompanied with SMC phenotypic transition in penile CC and impaired the erectile function eventually.These might,in turn,lead to variations in the SWQ values.It suggests that 2-D SWE may be a novel,noninvasive and effective approach that distinguishes penile CC lesions secondary to hyperlipidemia from normal.
文摘Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.
