IGF-1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: role of microRNA-1 and microRNA-133a.
IGF-1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: role of microRNA-1 and microRNA-133a.
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DOI：
10.1111/j.1582-4934.2011.01307.x
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发表时间：
2012-01
影响因子：
5.3
通讯作者：
Ren J
中科院分区：
文献类型：
--
作者：
Hua Y;Zhang Y;Ren J
本研究旨在研究胰岛素样生长因子-1（IGF-1）缺乏对腹主动脉缩窄（AAC）诱导的心脏几何和功能变化的影响，重点是microRNA-1，133 a和208，它们在心脏中特异性表达，并控制心脏肥大和应激依赖性心脏生长。对肝脏特异性IGF-1缺陷（LID）和C57/BL 6小鼠进行AAC。4周后评估超声心动图和心肌细胞功能。苏木精-伊红染色用于监测心肌形态。Western blot和实时荧光定量PCR分别检测蛋白和miR的表达。在IGF-1暴露之前用miR转染新生大鼠心肌细胞（NRCM）以启动细胞增殖。免疫组化和[3 H]亮氨酸掺入法检测细胞表面积和蛋白丰度。AAC处理的C57小鼠显示心室壁厚度增加，左心室舒张末期和收缩末期尺寸减小，心肌细胞缩短能力升高，所有这些在LID小鼠中均减弱。此外，IGF-1缺乏减轻了AAC诱导的心钠素、加塔结合蛋白4、葡萄糖转运蛋白4（GLUT 4）和Akt磷酸化的增加。相比之下，AAC治疗和IGF-1缺乏均不影响糖原合成酶激酶3b、雷帕霉素的哺乳动物靶点、Glut-4易位介体Akt底物160 kD（AS 160）和蛋白磷酸酶。在C57小鼠中，miR-1和-133a（但不是miR-208）的水平被AAC显著减弱，但不是LID小鼠。miR-1和-133a的转染消除了NRCM中IGF-1诱导的肥大反应。我们的数据表明，IGF-1缺乏通过减轻左心室压力超负荷时miR-1和miR-133 a的下调来延缓AAC诱导的心脏肥大和收缩变化。
This study was designed to examine the impact of insulin-like growth factor-1 (IGF-1) deficiency on abdominal aortic constriction (AAC)-induced cardiac geometric and functional changes with a focus on microRNA-1, 133a and 208, which are specially expressed in hearts and govern cardiac hypertrophy and stress-dependent cardiac growth. Liver-specific IGF-1-deficient (LID) and C57/BL6 mice were subject to AAC. Echocardiographic and cardiomyocyte function were assessed 4 wks later. Haematoxylin and eosin staining was used to monitor myocardial morphology. Western blot and real-time PCR were used to detect protein and miR expression, respectively. Neonatal rat cardiomyocytes (NRCMs) were transfected with miRs prior to IGF-1 exposure to initiate cell proliferation. Immunohistochemistry and [3H] Leucine incorporation were used to detect cell surface area and protein abundance. C57 mice subject to AAC displayed increased ventricular wall thickness, decreased left ventricular end diastolic and end systolic dimensions and elevated cardiomyocyte shortening capacity, all of which were attenuated in LID mice. In addition, IGF-1 deficiency mitigated AAC-induced increase in atrial natriuretic factor, GATA binding protein 4, glucose transporter 4 (GLUT4) and Akt phosphorylation. In contrast, neither AAC treatment nor IGF-1 deficiency affected glycogen synthase kinase 3b, mammalian target of rapamycin, the Glut-4 translocation mediator Akt substrate of 160 kD (AS160) and protein phosphatase. Levels of miR-1 and -133a (but not miR-208) were significantly attenuated by AAC in C57 but not LID mice. Transfection of miR-1 and -133a obliterated IGF-1-induced hypertrophic responses in NRCMs. Our data suggest that IGF-1 deficiency retards AAC-induced cardiac hypertrophic and contractile changes via alleviating down-regulation of miR-1 and miR-133a in response to left ventricular pressure overload.
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DOI：
10.1359/jbmr.090723
发表时间：
2010-02
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Fritton JC;Emerton KB;Sun H;Kawashima Y;Mejia W;Wu Y;Rosen CJ;Panus D;Bouxsein M;Majeska RJ;Schaffler MB;Yakar S
通讯作者：
Yakar S
影响因子：
11.8
作者：
Liu, ZP;Wang, ZG;Olson, EN
通讯作者：
Olson, EN
影响因子：
7.7
作者：
Funai K;Cartee GD
通讯作者：
Cartee GD
影响因子：
5.3
作者：
Barbier, Jerome;Dutertre, Martin;Auboeuf, Didier
通讯作者：
Auboeuf, Didier
影响因子：
37.8
作者：
ITO, H;HIROE, M;MARUMO, F
通讯作者：
MARUMO, F