The double face of miR-320: cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction.
The double face of miR-320: cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction.
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miR-320 的双面：心肌细胞来源的 miR-320 恶化，而成纤维细胞来源的 miR-320 可以预防横主动脉缩窄引起的心力衰竭
DOI：
10.1038/s41392-020-00445-8
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发表时间：
2021-02-18
影响因子：
39.3
通讯作者：
Wang DW
中科院分区：
文献类型：
--
作者：
Zhang X;Yuan S;Li H;Zhan J;Wang F;Fan J;Nie X;Wang Y;Wen Z;Chen Y;Chen C;Wang DW
microRNAs（miRNAs）在心力衰竭（HF）的病理生理过程中异常表达。然而，HF期间某种miRNA在不同心脏细胞类型中的功能却很少报道，这可能被它对心脏的地球仪效应所掩盖。本研究应用Langendorff细胞分离系统从横主动脉缩窄（TAC）诱导的小鼠中分离心肌细胞（CM）和心脏成纤维细胞（CF）。在TAC小鼠的整个心脏组织中观察到miR-320表达的轻微增加。有趣的是，在不同时间点，TAC小鼠的CM中miR-320显着升高，但CF中miR-320却降低。然后，使用具有细胞类型特异性启动子的重组腺相关病毒9来操纵miR-320在体内的表达。体外和体内实验均显示，在CM中过表达miR-320加重心功能不全，而在CF中过表达miR-320减轻心脏纤维化和肥大。在机制上，下游信号通路分析显示miR-320可分别通过靶向CM和CF中的PLEKHM 3和IFITM 1诱导各种效应。此外，miR-320介导的作用可以通过CM中的PLEKHM 3重新表达或CF中的IFITM 1重新表达而消除。有趣的是，miR-320处理的CF能够间接影响CM功能，但反之亦然。同时，上游信号通路分析表明，miR-320的表达和衰减速率受到Ago 2的严格操纵，Ago 2分别由一组在CM和CF中特异性表达的细胞类型特异性TF调控。总之，我们证明了miR-320在HF进展过程中在心脏的各种细胞类型中发挥不同的功能。
MicroRNAs (miRNAs) are aberrantly expressed in the pathophysiologic process of heart failure (HF). However, the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported, which might be covered by the globe effects of it on the heart. In the current study, Langendorff system was applied to isolate cardiomyocytes (CMs) and cardiac fibroblasts (CFs) from transverse aortic constriction (TAC)-induced mice. Slight increase of miR-320 expression was observed in the whole heart tissue of TAC mice. Interestingly, miR-320 was significantly elevated in CMs but decreased in CFs from TAC mice at different time points. Then, recombinant adeno-associated virus 9 with cell-type-specific promoters were used to manipulate miR-320 expressions in vivo. Both in vitro and in vivo experiments showed the miR-320 overexpression in CMs exacerbated cardiac dysfunction, whereas overexpression of miR-320 in CFs alleviated cardiac fibrosis and hypertrophy. Mechanically, downstream signaling pathway analyses revealed that miR-320 might induce various effects via targeting PLEKHM3 and IFITM1 in CMs and CFs, respectively. Moreover, miR-320 mediated effects could be abolished by PLEKHM3 re-expression in CMs or IFITM1 re-expression in CFs. Interestingly, miR-320 treated CFs were able to indirectly affect CMs function, but not vice versa. Meanwhile, upstream signaling pathway analyses showed that miR-320 expression and decay rate were rigorously manipulated by Ago2, which was regulated by a cluster of cell-type-specific TFs distinctively expressed in CMs and CFs, respectively. Together, we demonstrated that miR-320 functioned differently in various cell types of the heart during the progression of HF.
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影响因子：
37.8
作者：
Heymans, Stephane;Corsten, Maarten F.;Schroen, Blanche
通讯作者：
Schroen, Blanche
影响因子：
7.8
作者：
Min KW;Zealy RW;Davila S;Fomin M;Cummings JC;Makowsky D;Mcdowell CH;Thigpen H;Hafner M;Kwon SH;Georgescu C;Wren JD;Yoon JH
通讯作者：
Yoon JH
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.
影响因子：
29
作者：
Liu, Xiaojun;Xiao, Junjie;Rosenzweig, Anthony
通讯作者：
Rosenzweig, Anthony
影响因子：
5.1
作者：
Piras, B. A.;Tian, Y.;French, B. A.
通讯作者：
French, B. A.