Btg1 and Btg2 regulate neonatal cardiomyocyte cell cycle arrest

Velayutham, Nivedhitha; Calderon, Maria Uscategui; Alfieri, Christina M.; Padula, Stephanie L.; Leeuwen, Frank N. van; Scheijen, Blanca; Yutzey, Katherine E.

doi:10.1016/j.yjmcc.2023.03.016

Cited by 2 publications

(2 citation statements)

References 45 publications

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“…In addition, the molecular cell cycle control system of cardiomyocytes involves proto-oncogenes and tumor suppressors, and regulation of these genes to induce cell cycle re-entry may result in uncontrolled cardiomyocyte proliferation and even tumorigenesis, and also may lead to cardiac dysfunction in the long term [ 67 , 177 ]. For example, transient overexpression of Oct4, Sox2, Klf4, and c-Myc (OSKM) in adult mouse cardiomyocytes induces cell cycle re-entry and promotes non-tumorigenic cardiac regeneration, whereas prolonged expression of OSKM leads to cardiac tumor formation [ 36 ].…”

Section: Challenges In Cardiac Regeneration Researchmentioning

confidence: 99%

Targeting cardiomyocyte cell cycle regulation in heart failure

Zhu,

Yuan,

Krishnan

2024

Basic Res Cardiol

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Heart failure continues to be a significant global health concern, causing substantial morbidity and mortality. The limited ability of the adult heart to regenerate has posed challenges in finding effective treatments for cardiac pathologies. While various medications and surgical interventions have been used to improve cardiac function, they are not able to address the extensive loss of functioning cardiomyocytes that occurs during cardiac injury. As a result, there is growing interest in understanding how the cell cycle is regulated and exploring the potential for stimulating cardiomyocyte proliferation as a means of promoting heart regeneration. This review aims to provide an overview of current knowledge on cell cycle regulation and mechanisms underlying cardiomyocyte proliferation in cases of heart failure, while also highlighting established and novel therapeutic strategies targeting this area for treatment purposes.

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Section: Challenges In Cardiac Regeneration Researchmentioning

confidence: 99%

Targeting cardiomyocyte cell cycle regulation in heart failure

Zhu,

Yuan,

Krishnan

2024

Basic Res Cardiol

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“…BTG2 , part of the BTG/Tob family, regulates the cell cycle and various cellular activities [ 11 ]. As the first protein identified in BTG/Tob family, BTG2 possesses the ability to promote programmed cell death or survival [ 12 ]. Initially studied as an antioncogene [ 13 – 16 ], recent research has linked BTG2 to non-tumor conditions, including retinal microvascular endothelial cell proliferation [ 17 ], impaired blood pressure control and proteinuria [ 18 ], suggesting its potential importance in DKD.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease

Pan,

Teng,

Wang

et al. 2024

BMC Med Genomics

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Objective To investigate the role of BTG2 in periodontitis and diabetic kidney disease (DKD) and its potential underlying mechanism. Methods Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively. Results Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2’s relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3. Conclusion Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.

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Btg1 and Btg2 regulate neonatal cardiomyocyte cell cycle arrest

Cited by 2 publications

References 45 publications

Targeting cardiomyocyte cell cycle regulation in heart failure

Targeting cardiomyocyte cell cycle regulation in heart failure

Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease

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