Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling.
Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling.
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DOI：
10.1038/s41467-017-01737-4
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发表时间：
2017-11-20
影响因子：
16.6
通讯作者：
Engelhardt S
中科院分区：
文献类型：
--
作者：
Sassi Y;Avramopoulos P;Ramanujam D;Grüter L;Werfel S;Giosele S;Brunner AD;Esfandyari D;Papadopoulou AS;De Strooper B;Hübner N;Kumarswamy R;Thum T;Yin X;Mayr M;Laggerbauer B;Engelhardt S
慢性心脏应激可引起病理性心肌肥大和纤维化。microRNA-29 （miR-29）家族已被发现可以防止各种器官中胶原蛋白的过度表达，特别是通过其在成纤维细胞中的功能。在这里，我们发现miR-29促进心肌细胞的病理性肥大和整体心功能障碍。在心脏压力过载的小鼠模型中，miR-29的整体遗传缺失或anti - ir -29输注可防止心脏肥大和纤维化并改善心功能。在体内心肌细胞中靶向缺失miR-29也可以防止心脏肥大和纤维化，这表明miR-29在心肌细胞中的功能优于在非心肌细胞类型中的功能。在机制上，我们发现心肌细胞miR-29通过直接靶向四个通路因子来抑制Wnt信号。我们的数据表明，细胞或组织特异性的抗mir -29递送可能对病理性心脏重构和纤维化具有治疗价值。众所周知，MicroRNA-29可以减少成纤维细胞的胶原生成，从而抑制各种器官的纤维化。在这里，Sassi等人表明，miR-29也可以通过其在心肌细胞中的作用增强纤维化信号传导和心脏的病理性肥大。
Chronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium. The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts. Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction. In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function. Targeted deletion of miR-29 in cardiac myocytes in vivo also prevents cardiac hypertrophy and fibrosis, indicating that the function of miR-29 in cardiac myocytes dominates over that in non-myocyte cell types. Mechanistically, we found cardiac myocyte miR-29 to de-repress Wnt signaling by directly targeting four pathway factors. Our data suggests that, cell- or tissue-specific antimiR-29 delivery may have therapeutic value for pathological cardiac remodeling and fibrosis. MicroRNA-29 is known to reduce collagen production in fibroblasts thereby inhibiting fibrosis in various organs. Here, Sassi et al. show that miR-29 can also enhance fibrotic signalling and pathological hypertrophy of the heart through its action in cardiomyocytes.
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影响因子：
3.7
作者：
Liao JY;Ma LM;Guo YH;Zhang YC;Zhou H;Shao P;Chen YQ;Qu LH
通讯作者：
Qu LH
DOI：
10.1165/rcmb.2010-0323oc
发表时间：
2011-08-01
影响因子：
6.4
作者：
Cushing, Leah;Kuang, Ping Ping;Lue, Jining
通讯作者：
Lue, Jining
DOI：
10.1152/ajprenal.00287.2012
发表时间：
2013-05-01
影响因子：
4.2
作者：
Fang, Yi;Yu, Xiaofang;Ding, Xiaoqiang
通讯作者：
Ding, Xiaoqiang
影响因子：
20.1
作者：
Abonnenc, Melanie;Nabeebaccus, Adam A.;Mayr, Manuel
通讯作者：
Mayr, Manuel
影响因子：
3.7
作者：
Kauffman L;Balatti V;Cascione L;Fadda P;Racke F;Santhanam R;Costinean S
通讯作者：
Costinean S