Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats

Deng, Shengqiong; Zhao, Qian; Zhou, Xianjin; Zhang, Lin; Bao, Luer; Zhen, Lixiao; Zhang, Yuzhen; Fan, Huimin; Liu, Zhongmin; Yu, Zuoren

doi:10.3390/ijms17060875

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…Emerging evidence has demonstrated that non-coding miRNAs are capable of maintaining cardiac organ homeostasis and repairing injured heart in adult mammals. 6 , 24 , 25 , 26 A recent publication reported miR-128 serving as a critical regulator of endogenous cardiomyocyte proliferation. 36 Deletion of miR-128 promoted cell cycle re-entry in adult cardiomyocytes, and thereby reduced the levels of fibrosis and attenuated cardiac dysfunction in response to MI.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study on miRNA screening in cardiomyocytes revealed the enrichment of miR-708 and miR-301a in the heart of neonatal rats and mice. 2 , 26 miR-708 has been demonstrated to promote differentiation of cardiac progenitor cells and promote cardiac myocyte proliferation. 2 , 26 However, the function of miR-301a in cardiomyocytes remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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miR-301a-PTEN-AKT Signaling Induces Cardiomyocyte Proliferation and Promotes Cardiac Repair Post-MI

Zhen

Zhao

et al. 2020

Molecular Therapy - Nucleic Acids

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Adult hearts are hard to recover after cardiac injury due to the limited proliferative ability of cardiomyocytes. Emerging evidence indicates the induction of cell cycle reentry of cardiomyocytes by special treatment or stimulation, which offers adult heart regenerative potential. Herein, a microRNA (miRNA) screening in cardiomyocytes identified miR-301a enriched specially in the neonatal cardiomyocytes from rats and mice. Overexpression of miR-301a in primary neonatal cardiomyocytes and H9C2 cells induced G 1 /S transition of the cell cycle, promoted cellular proliferation, and protected cardiomyocytes against hypoxia-induced apoptosis. Adeno-associated virus (AAV)9-mediated cardiac delivery of miR-301a to the mice model with myocardial infarction (MI) dramatically promoted cardiac repair post-MI in vivo . Phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was confirmed to mediate miR-301a-induced cell proliferation in cardiomyocytes. Loss of function of PTEN mimicked the miR-301a-induced phenotype, while gain of function of PTEN attenuated the miR-301a-induced cell proliferation in cardiomyocytes. Application of RG7440, a small molecule inhibitor of AKT, blocked the function of miR-301a in cardiomyocytes. The current study revealed a miRNA signaling in inducing the cell cycle reentry of cardiomyocytes in the injured heart, and it demonstrated the miR-301a/PTEN/AKT signaling as a potential therapeutic target to reconstitute lost cardiomyocytes in mammals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-301a-PTEN-AKT Signaling Induces Cardiomyocyte Proliferation and Promotes Cardiac Repair Post-MI

Zhen

Zhao

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Thus, we think it is more likely that miR-708 may reactivate the quiescent progenitor cells and promote proliferation of the freshly differentiated cardiomyocytes in adult hearts. Although this has not been demonstrated yet by experimental assays in vivo , our previous work has indicated the differentiation induction of cardiac progenitor cells to cardiomyocytes in vitro 24 .…”

Section: Discussionmentioning

confidence: 87%

Neonatal Heart-Enriched miR-708 Promotes Proliferation and Stress Resistance of Cardiomyocytes in Rodents

Deng¹,

Zhao²,

Zhen³

et al. 2017

Theranostics

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Adult heart has limited potential for regeneration after pathological injury due to the limited cell proliferation of cardiomyocytes and the quiescent status of progenitor cells. As such, induction of cell-cycle reentry of cardiomyocytes is one of the key strategies for regeneration of damaged heart. In this study, a subset of miRNAs including miR-708 were identified to be much more abundant in the embryonic and neonatal cardiomyocytes than that in adult rodents. Overexpression of miR-708 promoted cellular proliferation of H9C2 cells or primary cardiomyocytes from neonatal rats or mice in vitro. Lipid nanoparticle delivery of miR-708 promoted myocardial regeneration and heart function recovery in vivo. In addition, miR-708 protected cardiomyocytes against stress-induced apoptosis under hypoxia or isoproterenol treatments. miR-708 inhibited the expression of MAPK14, which has been demonstrated arresting the cell cycle in cardiomyocytes. The cell proliferation-promoting function of miR-708 was dependent at least partly on the expression of MAPK14. These findings strengthen the potential of applying miRNAs to reconstitute lost cardiomyocytes in injured hearts, and may provide a novel miRNA candidate for promoting heart regeneration.

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“…Compared with non-progenitors, c-kit + CSCs display lower levels of miR-708, the expression of which is markedly upregulated upon CSC differentiation. Overexpression of miR-708 specifically promotes differentiation of CSCs to CMs [40]. In addition, the expression of miR-218 is upregulated during CSC differentiation into CMs.…”

Section: Mirna Signature and Function In Cardiac Stem Cellsmentioning

confidence: 99%

microRNAs and cardiac stem cells in heart development and disease

Meng

Zhang

2019

Drug Discovery Today

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Cumulative evidence has proven that proliferation, differentiation and migration of cardiac stem cells (CSCs) dominate early heart development and contribute to the later occurrence of heart disease. Among other mechanisms, microRNAs work as the 'fine-tuning' to modulate the levels of target genes in a specific cell type. The distinct microRNA signatures in CSCs reveal the stages and functions of CSCs. The focus of this review is to summarize recent knowledge advances in CSC proliferation, differentiation and migration and to discuss how microRNAs regulate these processes during heart development and in heart disease. Better understanding of microRNA regulation on CSCs under different situations will enable the unveiling of the mechanisms of heart disease and open new avenues in the therapeutic potentials of microRNA modulation to treat heart disease.

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Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats

Cited by 12 publications

References 25 publications

miR-301a-PTEN-AKT Signaling Induces Cardiomyocyte Proliferation and Promotes Cardiac Repair Post-MI

miR-301a-PTEN-AKT Signaling Induces Cardiomyocyte Proliferation and Promotes Cardiac Repair Post-MI

Neonatal Heart-Enriched miR-708 Promotes Proliferation and Stress Resistance of Cardiomyocytes in Rodents

microRNAs and cardiac stem cells in heart development and disease

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