The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy.
The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy.
复制标题
DOI：
10.1038/ncomms2090
复制
发表时间：
2012
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
心肌细胞的病理性生长（肥大）是心力衰竭发展的主要决定因素，心力衰竭是全球死亡的主要医学原因之一。在这里，我们表明microRNA（miRNA）-212/132家族调节心肌细胞中的心肌肥大和自噬。肥大刺激上调心肌细胞miR-212和miR-132的表达，这两者对于驱动心肌细胞肥大生长都是必要且足够的。miR-212/132基因敲除小鼠可避免压力超负荷诱导的心力衰竭，而miR-212/132家族的心肌细胞特异性过表达可导致小鼠病理性心脏肥大、心力衰竭和死亡。miR-212和miR-132都直接靶向抗肥大和促自噬FoxO 3转录因子，这些miRNA的过表达导致促肥大钙调磷酸酶/NFAT信号转导的过度激活和饥饿时自噬反应受损。miR-132的药理学抑制通过注射Escheromir挽救小鼠的心脏肥大和心力衰竭，为心力衰竭提供了可能的治疗方法。心力衰竭通常是心肌细胞病理性生长或心脏肥大的结果。Ucar及其同事在本文中报道了microRNAs miR-132和miR-212通过下调转录因子FoxO 3促进心肌肥大并抑制心肌细胞自噬。
Pathological growth of cardiomyocytes (hypertrophy) is a major determinant for the development of heart failure, one of the leading medical causes of mortality worldwide. Here we show that the microRNA (miRNA)-212/132 family regulates cardiac hypertrophy and autophagy in cardiomyocytes. Hypertrophic stimuli upregulate cardiomyocyte expression of miR-212 and miR-132, which are both necessary and sufficient to drive the hypertrophic growth of cardiomyocytes. MiR-212/132 null mice are protected from pressure-overload-induced heart failure, whereas cardiomyocyte-specific overexpression of the miR-212/132 family leads to pathological cardiac hypertrophy, heart failure and death in mice. Both miR-212 and miR-132 directly target the anti-hypertrophic and pro-autophagic FoxO3 transcription factor and overexpression of these miRNAs leads to hyperactivation of pro-hypertrophic calcineurin/NFAT signalling and an impaired autophagic response upon starvation. Pharmacological inhibition of miR-132 by antagomir injection rescues cardiac hypertrophy and heart failure in mice, offering a possible therapeutic approach for cardiac failure. Heart failure is often a consequence of pathological growth of cardiomyocytes or cardiac hypertrophy. Here Ucar and colleagues report that the microRNAs miR-132 and miR-212 promote cardiac hypertrophy and inhibit autophagy in cardiomyocytes by downregulating the transcription factor FoxO3.
登录
查看更多内容
影响因子：
20.1
作者：
Rao PK;Toyama Y;Chiang HR;Gupta S;Bauer M;Medvid R;Reinhardt F;Liao R;Krieger M;Jaenisch R;Lodish HF;Blelloch R
通讯作者：
Blelloch R
影响因子：
8
作者：
Aki, T;Yamaguchi, K;Mizukami, Y
通讯作者：
Mizukami, Y
DOI：
10.1073/pnas.0710228105
发表时间：
2008-02-12
影响因子：
11.1
作者：
Chen, Jian-Fu;Murchison, Elizabeth P.;Wang, Da-Zhi
通讯作者：
Wang, Da-Zhi
影响因子：
10.8
作者：
Kanamori, Hiromitsu;Takemura, Genzou;Minatoguchi, Shinya
通讯作者：
Minatoguchi, Shinya
影响因子：
20.1
作者：
Merkle, Sabine;Frantz, Stefan;Engelhardt, Stefan
通讯作者：
Engelhardt, Stefan