Circulation ResearchСHDAC3ػ
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ȫֲѾ“”ѧҽѧԺDr. Deqiang LiоŶ20227Circulation Research־ϽΪ“Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway”ѪоչĤHDAC3ͨmiR-322/miR-503̼Fgf9Igf2ļΪȱݵIJļṩµսԺͿ
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HDACѰȥø3һHDACijԱԴѰβлȥִͨﳡѧ߲ȫóHDAC3ɵ¼Դȱݺ̥ļԵHDAC3ȱʧȴж̬ͱӰǻڵЧעHDAC3ڷǼϸҼĹЧܶļҪоּ̽ѰHDAC3ĤеԼFgf9Igf2ıܵHDACsmiRsĵ
ͼ. The schematics of the working model
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1еĤHdac3ıļҪ
2HDAC3ĤϸֽǨǺҪ
3miR-322miR-503Fgf9Igf2ת¼
4HDAC3ͨmiR-322miR-503ıFgf9Igf2ת¼
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Figure 1. Epicardial deletion of Hdac3 resulted in hypoplasia of ventricular compact wall.
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Figure 2. Hdac3 deletion resulted in downregulation of Fgf9 and Igf2.
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оͼȷFgf9Igf2̭Ƿļϸֳ̭йϸEVHdac3óKOҺFgf9Igf2ϸ崦óͷE13.5ɢԭ̥ļϸEVKO崦óͷpH3ļϸٷֱȺļϸͲļϸֳźͨ·ERKữļKOFgf9Igf2ļϸֳȱݲʹp-FGFR1/p-IGFR1ЧעĤϸFgf9Igf2ṩļϸֳҪ
Figure 3. Supplementation of Fgf9 or Igf2 rescues CM proliferation defects.
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Figure 4. HDAC3 induces the expression of Fgf9 and Igf2 dependent on its deacetylase activity.
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FgfsIgfsıɱmiRsо߶ómiRͨģϵλɸѡmiR-322miR-503ģﴦóͷFgf9Igf2ıͨWestern blotһ֤miR-322 mimics/miR-503 mimicsóͷFgf9Igf2ʹmiR-322miR-503ģﴦóͷE13.5ļϸpH3ļϸİٷֱעmiR-322miR-503ļϸֳHDAC3ȥøԱRGFP966ʱmiR-322miR-503óͬϵE13.5 ekoҲӲ쵽miR-322miR-503ϵ֤ʵmiR-322miR-503ܹFgf9Igf2ļϸֳ
Figure 5.miR-322 and miR-503 repress the expression of Fgf9 and Igf2 and CM proliferation.
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Figure 6. Knockdown of miR-322 or miR-503 restores the expression of Fgf9 and Igf2.
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Figure 7. HDAC3 represses miR-322/miR-503 promoter activity.
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