典型文献
IMM-H007 attenuates isoprenaline-induced cardiac fibrosis through targeting TGFβ1 signaling pathway
文献摘要：
Upon chronic stress,β-adrenergic receptor activation induces cardiac fibrosis and leads to heart failure.The small molecule compound IMM-H007 has demonstrated protective effects in cardiovascular diseases via activation of AMP-activated protein kinase(AMPK).This study aimed to investigate IMM-H007 effects on cardiac fibrosis induced by β-adrenergic receptor activation.Because adenosine analogs also exert AMPK-independent effects,we assessed AMPK-dependent and-independent IMM-H007 effects in murine models of cardiac fibrosis.Continual subcutaneous injection of isoprenaline for 7 days caused cardiac fibrosis and cardiac dysfunction in mice in vivo.IMM-H007 attenuated isoprenaline-induced cardiac fibrosis,diastolic dysfunction,α-smooth muscle actin expression,and collagen Ⅰ deposition in both wild-type and AMPKα2-/-mice.Moreover,IMM-H007 inhibited transforming growth factor β1(TGFβ1)expression in wild-type,but not AMPKa2-/-mice.By contrast,IMM-H007 inhibited Smad2/3 signaling downstream of TGFβ1 in both wild-type and AMPKα2-/-mice.Surface plasmon resonance and molecular docking experiments showed that IMM-H007 directly interacts with TGFβ1,inhibits its binding to TGFβ type Ⅱ receptors,and downregulates the Smad2/3 signaling pathway downstream of TGFβ1.These findings suggest that IMM-H007 inhibits isoprenaline-induced cardiac fibrosis via both AMPKα2-dependent and-independent mechanisms.IMM-H007 may be useful as a novel TGFβ1 antagonist.
文献关键词：
中图分类号：
作者姓名：
Shuai-xing Wang;Ye-nan Feng;Shan Feng;Ji-min Wu;Mi Zhang;Wen-li Xu;You-yi Zhang;Hai-bo Zhu;Han Xiao;Er-dan Dong
作者机构：
Department of Cardiology and Institute of Vascular Medicine,Peking University Third Hospital,NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides,Key Laboratory of Molecular Cardiovascular Science,Ministry of Education,Beijing Key Laboratory of Cardiovascular Receptors Research,Beijing 100191,China;State Key Laboratory for Bioactive Substances and Functions of Natural Medicines,Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China
文献出处：
引用格式：
[1]Shuai-xing Wang;Ye-nan Feng;Shan Feng;Ji-min Wu;Mi Zhang;Wen-li Xu;You-yi Zhang;Hai-bo Zhu;Han Xiao;Er-dan Dong-.IMM-H007 attenuates isoprenaline-induced cardiac fibrosis through targeting TGFβ1 signaling pathway)[J].中国药理学报（英文版）,2022(10):2542-2549
A类：
H007,Continual,AMPKa2
B类：
IMM,attenuates,isoprenaline,induced,cardiac,fibrosis,through,targeting,TGF,signaling,pathway,Upon,chronic,stress,adrenergic,activation,induces,leads,heart,failure,small,molecule,compound,has,demonstrated,protective,effects,cardiovascular,diseases,via,activated,protein,kinase,This,study,aimed,investigate,by,Because,adenosine,analogs,also,exert,independent,assessed,murine,models,subcutaneous,injection,days,caused,dysfunction,mice,vivo,attenuated,diastolic,smooth,muscle,actin,expression,collagen,deposition,both,wild,type,Moreover,inhibited,transforming,growth,but,not,By,contrast,Smad2,downstream,Surface,plasmon,resonance,molecular,docking,experiments,showed,that,directly,interacts,inhibits,binding,receptors,downregulates,These,findings,suggest,mechanisms,may,be,useful,novel,antagonist
AB值：
0.454084
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