Natriuretic peptides and Forkhead O transcription factors act in a cooperative manner to promote cardiomyocyte cell cycle re-entry in the postnatal mouse heart.
Natriuretic peptides and Forkhead O transcription factors act in a cooperative manner to promote cardiomyocyte cell cycle re-entry in the postnatal mouse heart.
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亚钠肽和叉子o转录因子以合作的方式起作用，以促进产后小鼠心脏中的心肌细胞周期重新进入。
DOI：
10.1186/s12861-020-00236-y
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发表时间：
2021-02-03
影响因子：
--
通讯作者：
Tian Y
中科院分区：
文献类型：
--
作者：
Ali M;Liccardo D;Cao T;Tian Y
心肌细胞在胎儿期迅速增殖，但出生后不久即丧失增殖能力。然而，在细胞周期终末退出之前，小鼠出生后早期的心肌细胞经历另一轮细胞周期。虽然在出生后小鼠心脏中观察到心肌细胞中DNA合成增加的瞬时波，但描述心肌细胞细胞周期重新进入的分子机制仍然知之甚少。心房肽和B型利钠肽（ANP和BNP）在胚胎心室中大量表达。出生后，这两种基因的表达在心室肌中强烈降低。叉头O（FOXO）转录因子在胚胎和出生后的心室中都有表达。它们的转录活性对心肌细胞增殖有负面影响。在磷酸化后，FOXO易位至细胞质并且在转录上无活性。尽管有这些重要的发现，但在出生后早期，利钠肽和FOXO是否协同调节心肌细胞周期活性仍是未知数。我们观察到，在出生后的小鼠心脏心室的ANP和BNP的表达和磷酸化FOXO的水平瞬时增加，这与小鼠出生后早期心肌细胞周期重新进入的爆发相一致。细胞培养研究表明，ANP/BNP信号和FOXO协同促进新生小鼠心肌细胞的细胞周期活性。在ANP/BNP和显性负性FOXO（DN-FOXO）联合治疗中观察到的细胞周期活性增强主要通过利钠肽受体3（Npr 3）介导，DN-FOXO可以结合DNA上的FOXO识别位点，但不能激活转录。在小鼠中，在出生后的心脏中同时应用ANP和DN-FOXO重新激活了心肌细胞的细胞周期，导致实验性心肌梗死后瘢痕形成减少。我们的数据表明利钠肽和DN-FOXO在促进心肌细胞细胞周期活性和损伤后小鼠心脏修复和再生方面具有协同作用。在线版本包含补充材料，可通过10.1186/s12861-020-00236-y获得。
Cardiomyocytes proliferate rapidly during fetal life but lose their ability of proliferation soon after birth. However, before terminal withdrawal from the cell cycle, cardiomyocytes undergo another round of cell cycle during early postnatal life in mice. While a transient wave of increased DNA synthesis in cardiomyocyte has been observed in postnatal mouse hearts, the molecular mechanisms describing cardiomyocyte cell cycle re-entry remain poorly understood. Atrial and B-type natriuretic peptides (ANP and BNP) are abundantly expressed in embryonic heart ventricles. After birth, the expression of both genes is strongly reduced in the ventricular myocardium. Forkhead O (FOXO) transcription factors are expressed in both embryonic and postnatal heart ventricles. Their transcriptional activity negatively affects cardiomyocyte proliferation. Upon phosphorylation, FOXO is translocated to the cytoplasm and is transcriptionally inactive. Despite these important findings, it remains largely unknown whether natriuretic peptides and FOXO cooperatively play a role in regulating cardiomyocyte cell cycle activity during early postnatal life. We observed that the expression of ANP and BNP and the level of phosphorylated FOXO were transiently increased in the postnatal mouse heart ventricles, which coincided with the burst of cardiomyocyte cell cycle re-entry during early postnatal life in mice. Cell culture studies showed that ANP/BNP signaling and FOXO cooperatively promoted cell cycle activity in neonatal mouse cardiomyocytes. The enhanced cell cycle activity observed in combined treatment of ANP/BNP and dominant-negative FOXO (DN-FOXO), which can bind FOXO recognition sites on DNA but cannot activate transcription, was primarily mediated through natriuretic peptide receptor 3 (Npr3). In mice, simultaneous application of ANP and DN-FOXO in postnatal hearts reactivated cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction. Our data demonstrate the cooperative effects of natriuretic peptide and DN-FOXO on promoting cardiomyocyte cell cycle activity and mouse cardiac repair and regeneration after injury. The online version contains supplementary material available at 10.1186/s12861-020-00236-y.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1073/pnas.0510019103
发表时间：
2006-03-21
影响因子：
11.1
作者：
Langenickel, TH;Buttgereit, J;Bader, M
通讯作者：
Bader, M
影响因子：
4.8
作者：
Rena, G;Guo, SD;Cohen, P
通讯作者：
Cohen, P
影响因子：
5.5
作者：
O'Tierney, P. F.;Chattergoon, N. N.;Thornburg, K. L.
通讯作者：
Thornburg, K. L.
影响因子：
20.1
作者：
Evans-Anderson, Heather J.;Alfieri, Christina M.;Yutzey, Katherine E.
通讯作者：
Yutzey, Katherine E.