Transforming growth factor-β (TGF-β) is a multifunctional peptide growth factor with a wide range of effects. TGF-β signals are conveyed through cell-surface serine/threonine kinase receptors to the downstream cyto...Transforming growth factor-β (TGF-β) is a multifunctional peptide growth factor with a wide range of effects. TGF-β signals are conveyed through cell-surface serine/threonine kinase receptors to the downstream cytoplasmic mediators, known as Smads proteins. Receptor-regulated Smads become phosphorylated by activated type Ⅰ receptors and form heteromeric complexes with a common Smad-Smad4, which translocates into the nucleus to regulate gene transcription. Inhibitory Smads inhibit the activation of receptor-regulated Smads. There are positive, negative and feedback regulations in the Smads mediated TGF-β signaling pathway.展开更多
文摘Transforming growth factor-β (TGF-β) is a multifunctional peptide growth factor with a wide range of effects. TGF-β signals are conveyed through cell-surface serine/threonine kinase receptors to the downstream cytoplasmic mediators, known as Smads proteins. Receptor-regulated Smads become phosphorylated by activated type Ⅰ receptors and form heteromeric complexes with a common Smad-Smad4, which translocates into the nucleus to regulate gene transcription. Inhibitory Smads inhibit the activation of receptor-regulated Smads. There are positive, negative and feedback regulations in the Smads mediated TGF-β signaling pathway.
文摘目的观察黄芪多糖(astragalus polysaccharide,APS)通过转化生长因子-β1(transforming growth Factor-β1,TGF-β1)/Smads信号传导通路对异丙肾上腺素(isoproterenol,ISO)诱导的大鼠心肌纤维化的影响。方法 SD(Sprague-Dawley)大鼠分别ig给予APS 400和800 mg·kg^(-1),24 h后ip给予ISO 10 mg·kg-1,连续14 d。BL420型四道生理记录仪记录左心室收缩最大压(left ventricular systolic pressure,LVSP)及左心室舒张末压(left ventricular end-diastolic pressure,LVEDP),左心室最大收缩、舒张期压力微分(maximum rate of rise/decrease of LVSP,±dp/dtmax)全心质量指数(heart mass index,HMI)和左心室质量指数(left ventricular mass index,LVMI);苏木精-伊红染色法(hematoxylin-eosin staining,HE)染色和天狼星红染色,在光镜下观察其心肌形态并测定其胶原容积积分(collagenvol-umefraction,CVF);Western蛋白印迹法测定TGF-β1和Smads蛋白的表达;RT-PCR测定TGF-β1mRNA的表达;ELISA测定I型前胶原羧基前肽(propeptide of type I procollagen,PICP)及其抑制物I型胶原交联羧基末端肽(type I collagen carboxy-terminal cross-linked peptide,ICTP)的含量。结果与正常组相比,模型组大鼠心功能指数显著上升(P<0.01);左心室质量指数显著上升(P<0.01);CVF显著上升(P<0.01);PICP/ICTP明显上升,Smad2/3,Smad4及TGF-β1的蛋白含量显著上升(P<0.01);Smad 7蛋白含量显著下降(P<0.01);TGF-β_1 mRNA的表达明显升高(P<0.01)。给药APS后,心功能指数可明显下降(P<0.05),左心室质量指数显著上升(P<0.05),CVF减少(P<0.05),Smad2/3(P<0.05),Smad4及TGF-β1的蛋白含量及mRNA的表达均下降(P<0.05),Smad7的蛋白含量上升(P<0.05)。通过ELISA测定PICP/ICTP能反映与TGF-β_1表达呈正相关性,其比值明显下降(P<0.05)。结论 APS对ISO诱导的心肌纤维化有一定的防治作用,其机制与抑制TGF-β_1/Smads通路相关。
