Role of PTEN-less in cardiac injury, hypertrophy and regeneration

Liang, Tian; Gao, Feng; Chen, Jinghai

doi:10.1186/s13619-021-00087-3

Cited by 21 publications

(21 citation statements)

References 101 publications

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“…At the same time, PI3K and Akt are also the key to promote the survival of cardiomyocytes and give full play to the function of cardiomyocytes [ 12 ]. The blocking of activation of this signaling pathway mainly relies on the negative regulation of chromosome 10 phosphatase and tensin homolog (PTEN) deletion, which dephosphorylates PIP3 to PIP2 [ 13 , 14 ]. In addition, there are some signal transduction pathways that also play a key role in cell proliferation, transformation, and apoptosis, such as the extracellular signal-regulated kinase (ERK1/2) pathway [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…It must be emphasized that PTEN, as a dual-specific phosphatase, can dephosphorylate lipids and proteins on serine, threonine, and tyrosine residues in many tissues including heart and cardiomyocytes and widely expressed in cells [ 13 ]. In recent years, with the deepening of research on PTEN, more and more biological functions have been recognized, including embryonic development, tumorigenesis, and heart growth.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Ghrelin Intervention on the Ras/ERK Pathway in the Regulation of Heart Failure by PTEN

Zhao

Sun

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To study the possible mechanism of ghrelin in heart failure and how it works. Method. In vitro results demonstrated that ghrelin alleviates cardiac function and reduces myocardial fibrosis in rats with heart failure. Moreover, ghrelin intervention increased PTEN expression level and reduced ERK, c-jun, and c-Fos expression level; in vivo experiments demonstrated that ghrelin intervention reduces mast memory expression and increases cardiomyocyte surface area, PTEN expression level, ERK, c-jun, c-Fos expression level, and cell surface area, while ERK blockade suppresses mast gene expression and reduces cell surface area. Results. In vitro experimental results prove that we have successfully constructed a rat model related to heart failure, and ghrelin can alleviate the heart function of heart failure rats and reduce myocardial fibrosis. In addition, ghrelin is closely related to the decrease of the expression levels of ERK, c-jun, and c-Fos, but it can also increase the expression of PTEN in the rat model; in vivo experiments proved that we successfully constructed an in vitro cardiac hypertrophy model, and the intervention of ghrelin would reduce the expression of hypertrophic memory and increase the surface area of cardiomyocytes, increase the expression level of PTEN, and reduce the expression levels of ERK, c-jun, and c-Fos, while the blockade of PTEN will increase the expression of hypertrophy genes and increase the cell surface area, while the blockade of ERK will increase the expression of hypertrophic genes, which in turn will make the cell surface area reducing. Conclusion. Ghrelin inhibits the phosphorylation and nuclear entry of ERK by activating PTEN, thereby controlling the transcription of hypertrophic genes, improving myocardial hypertrophy, and enhancing cardiac function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Ghrelin Intervention on the Ras/ERK Pathway in the Regulation of Heart Failure by PTEN

Zhao

Sun

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Several researches reported the increased expression of PTEN in MI ( Parajuli et al, 2012 ; Feng et al, 2020 ), which were consistent with our results. As PTEN was reported to play roles in cell apoptosis and survival through PI3K/AKT pathway ( Wu et al, 2006 ; Mocanu and Yellon, 2007 ), PTEN reducing became a potential therapeutic target for increasing myocardial survival ( Oudit et al, 2004 ; Liang et al, 2021b ). So PTEN is a very promising candidate hub gene for further research and maybe potential therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Construction and Bioinformatics Analysis of circRNA-miRNA-mRNA Network in Acute Myocardial Infarction

Zhou

Wang

et al. 2022

Front. Genet.

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Background: Acute myocardial infarction (AMI) is one of the main fatal diseases of cardiovascular diseases. Circular RNA (circRNA) is a non-coding RNA (ncRNA), which plays a role in cardiovascular disease as a competitive endogenous RNA (ceRNA). However, their role in AMI has not been fully clarified. This study aims to explore the mechanism of circRNA-related ceRNA network in AMI, and to identify the corresponding immune infiltration characteristics.Materials and Methods: The circRNA (GSE160717), miRNA (GSE24548), and mRNA (GSE60993) microarray datasets of AMI were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified by the “limma” package. After integrating the circRNA, miRNA and mRNA interaction, we constructed a circRNA-miRNA-mRNA network. The “clusterProfiler” package and String database were used for functional enrichment analysis and protein-protein interaction (PPI) analysis, respectively. After that, we constructed a circRNA-miRNA-hub gene network and validated the circRNAs and mRNAs using an independent dataset (GSE61144) as well as qRT-PCR. Finally, we used CIBERSORTx database to analyze the immune infiltration characteristics of AMI and the correlation between hub genes and immune cells.Results: Using the “limma” package of the R, 83 DEcircRNAs, 54 DEmiRNAs, and 754 DEmRNAs were identified in the microarray datasets of AMI. Among 83 DEcircRNAs, there are 55 exonic DEcircRNAs. Then, a circRNA-miRNA-mRNA network consists of 21 DEcircRNAs, 11 DEmiRNAs, and 106 DEmRNAs were predicted by the database. After that, 10 hub genes from the PPI network were identified. Then, a new circRNA-miRNA-hub gene network consists of 14 DEcircRNAs, 7 DEmiRNAs, and 9 DEmRNAs was constructed. After that, three key circRNAs (hsa_circ_0009018, hsa_circ_0030569 and hsa_circ_0031017) and three hub genes (BCL6, PTGS2 and PTEN) were identified from the network by qRT-PCR. Finally, immune infiltration analysis showed that hub genes were significantly positively correlated with up-regulated immune cells (neutrophils, macrophages and plasma cells) in AMI.Conclusion: Our study constructed a circRNA-related ceRNA networks in AMI, consists of hsa_circ_0031017/hsa-miR-142-5p/PTEN axis, hsa_circ_0030569/hsa-miR-545/PTGS2 axis and hsa_circ_0009018/hsa-miR-139-3p/BCL6 axis. These three hub genes were significantly positively correlated with up-regulated immune cells (neutrophils, macrophages and plasma cells) in AMI. It helps improve understanding of AMI mechanism and provides future potential therapeutic targets.

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“…Myocardial infarction (MI) causes irreversible myocardial damage and remains the main drive for heart failure with limited primary and secondary prevention measures available (Chang et al, 2021 ; Yang et al, 2019a ; Alam et al, 2021 ). The poor ability of mammalian cardiomyocytes to regenerate and proliferate serves as the major factor for post-MI adverse myocardial remodeling and function (Alam et al, 2021 ; Liang et al, 2021 ; Xiong, 2020 ; Davidson et al, 2021 ). Ample efforts including drug therapy and percutaneous coronary intervention (PCI) procedures in post-MI care help to lower post MI-associated cardiac morbidity and mortality (Zhou et al, 2018 ; Bhatt et al, 2022 ; Zhang & Ren, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…To this end, this study was designed to evaluate the role of autophagy insufficiency using Beclin1 haploinsufficiency on MSCs-induced beneficial effect against post-MI injury. Given that stem cell therapy may execute its beneficial response through regulation of apoptosis and inflammation (Liang et al, 2021 ; Davidson et al, 2021 ; Parizadeh et al, 2019 ; Ouyang & Wei, 2021 ), levels of apoptosis and inflammation were monitored in post-MI hearts with or without MSCs transplantation. CM-Dil labelled MSCs were transplanted into recipient hearts immediately after ligation of left coronary artery.…”

Section: Introductionmentioning

confidence: 99%

Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction

et al. 2022

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Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/−) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN+/− recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca2+ were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN+/− mice. MI decreased intracellular Ca2+ rise and decay in response to electrical stimuli without affecting resting intracellular Ca2+, which were reconciled by MSCs in WT but not BECN+/− mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN+/− mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation.

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Role of PTEN-less in cardiac injury, hypertrophy and regeneration

Cited by 21 publications

References 101 publications

Effect of Ghrelin Intervention on the Ras/ERK Pathway in the Regulation of Heart Failure by PTEN

Effect of Ghrelin Intervention on the Ras/ERK Pathway in the Regulation of Heart Failure by PTEN

Construction and Bioinformatics Analysis of circRNA-miRNA-mRNA Network in Acute Myocardial Infarction

Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction

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