YAP1 Contributes to The Development of Contractile Force and Sarcomere Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes DOI
Vladimír Vinarský, Stefania Pagliari, Fabiana De Martino

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 5, 2024

Abstract Background Perspective regenerative therapies for injured myocardium focus on reactivating developmental processes to regenerate damaged contractile tissue. In animal models, the Hippo pathway was shown improve heart regeneration after myocardial infarction, possibly by expanding pool of cardiomyocytes. We hypothesized that activating pathway’s downstream effector, Yes Associated Protein (YAP1), may have effects beyond promoting proliferation in human therefore investigated how YAP1 influences cardiomyocyte maturation, sarcomere structure, electrophysiological properties, their response mechanical stimuli, intracellular Ca 2+ ″ dynamics and force development using models cardiomyocytes derived from pluripotent stem cells. Methods employed genetic deficient embryonic induced cells, differentiation, compliant cultivation substrates, actuation, ECM deposition, super resolution microscopy, measurements engineered tissues (EHTs) characterize deficiency during maturation. also used full length re- expression rescue contracting Results contributes participates formation alignment myofibrils, as well maturation properties. The net effect is inability respond physiological stimuli compensatory growth resulting reduced development. Additionally, reactivation leads myofibril Conclusions This research demonstrates activity essential promote contractility, inducing stimuli.

Язык: Английский

RNA-binding proteins in cardiovascular biology and disease: the beat goes on DOI
Mirko Völkers, Thomas Preiß, Matthias W. Hentze

и другие.

Nature Reviews Cardiology, Год журнала: 2024, Номер 21(6), С. 361 - 378

Опубликована: Янв. 2, 2024

Язык: Английский

Процитировано

14
Advanced Microarrays as Heterogeneous Force‐Remodeling Coordinator to Orchestrate Nuclear Configuration and Force‐Sensing Mechanotransduction in Stem Cells DOI Creative Commons
Nana Wang,

Yan Hou,

Xin Lin

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Integrin and focal adhesion can regulate cytoskeleton distribution to govern actin-related force remodeling play an important role in nuclear configuration force-sensing mechanotransduction of stem cells. However, further exploration the interaction between actinin complex myosin, kinetics, molecular mechanism structures nucleate within engineered cells is vague. An extensive comprehension cell morphogenesis, remodeling, essential reveal basic physical principles polymerization force-related signaling delivery. Advanced microarrays are designed determine heterogeneous morphology behaviors The heterogeneity from transferred into nuclei by evaluation Lamins, YAP, BrdU expression. Tuning activation proteins nucleators adjust mechanics may be underlying change response its physiological microarrayed

Язык: Английский

Процитировано

1
Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis DOI Creative Commons
Cong Chen, Jie Wang,

Shan Zhang

и другие.

Redox Biology, Год журнала: 2024, Номер 76, С. 103321 - 103321

Опубликована: Авг. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Язык: Английский

Процитировано

6
Fibrotic extracellular matrix impacts cardiomyocyte phenotype and function in an iPSC-derived isogenic model of cardiac fibrosis DOI Creative Commons
Francesco Niro, Soraia Fernandes, Marco Cassani

и другие.

Translational research, Год журнала: 2024, Номер 273, С. 58 - 77

Опубликована: Июль 16, 2024

Cardiac fibrosis occurs following insults to the myocardium and is characterized by abnormal accumulation of non-compliant extracellular matrix (ECM), which compromises cardiomyocyte contractile activity eventually leads heart failure. This phenomenon driven activation cardiac fibroblasts (cFbs) myofibroblasts results in changes ECM biochemical, structural mechanical properties. The lack predictive vitro models has so far hampered search for innovative treatments, as most cellular-based reductionist do not take into account leading role cues driving progression pathology. Here, we devised a single-step decellularization protocol obtain thoroughly characterize biochemical micro-mechanical properties secreted activated cFbs differentiated from human induced pluripotent stem cells (iPSCs). We iPSC-derived myofibroblast phenotype tuning basic fibroblast growth factor (bFGF) transforming beta 1 (TGF-β1) signalling confirmed that acquired key features phenotype, like SMAD2/3 nuclear shuttling, formation aligned alpha-smooth muscle actin (α−SMA)-rich stress fibres increased focal adhesions (FAs) assembly. Next, used Mass Spectrometry, nanoindentation, scanning electron confocal microscopy unveil characteristic composition visco-elastic abundant, collagen-rich deposited vitro. Finally, demonstrated fibrotic activates mechanosensitive pathways cardiomyocytes, impacting on their shape, sarcomere assembly, calcium handling thus propose bio-inspired decellularized matrices animal-free, isogenic culture substrates recapitulating pathophysiological occurring at cellular level during fibrosis.

Язык: Английский

Процитировано

4
Whole tissue proteomic analyses of cardiac ATTR and AL unveil mechanisms of tissue damage DOI

Brian C. Netzel,

M. Cristine Charlesworth, Kenneth L. Johnson

и другие.

Amyloid, Год журнала: 2025, Номер unknown, С. 1 - 9

Опубликована: Янв. 8, 2025

Background Cardiac AL and ATTR are potentially fatal cardiomyopathies. Current therapies do not address mechanisms of tissue dysfunction because these remain unknown. Our prior work focused on the amyloid plaque proteome, which may capture tissue-wide proteomic alterations.

Язык: Английский

Процитировано

0
Alternative RNA Splicing in Cardiac Diseases DOI Creative Commons
Junli Gao, Yanan Zhang,

Meiyu Hu

и другие.

Cardiovascular Innovations and Applications, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 1, 2025

Alternative splicing (AS), a critical process for gene expression regulation, allows single precursor RNA to produce multiple transcript variants. Alterations in exon exclusion, intron retention, or the selection of alternative splice sites modify isoforms, which can consequently affect molecules, including mRNA and non-coding RNAs, terms their localization, overall function. In cardiovascular system, AS transcripts sarcomere, ion channel, cell signaling protein genes, as well long contribute development diseases. addition, hereditary heart-related diseases are caused by mutations associated with AS. this review, we discuss how regulates individual genes global biological processes, thereby diversifying patterns target playing roles We also review application design innovative therapeutic approaches.

Язык: Английский

Процитировано

0
Immediate early splicing controls translation in activated T-cells and is mediated by hnRNPC2 phosphorylation DOI Creative Commons
M Dróźdź, Luíza Zuvanov,

Gopika Sasikumar

и другие.

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

The fast and transient induction of immediate early genes orchestrates the cellular response to various stimuli. These stimuli trigger phosphorylation cascades that promote gene transcription independent de novo protein synthesis. Here we show same also target splicing machinery, inducing an analogous switch call (IES). We characterize hnRNPC2-controlled IES, which depends on MEK-ERK pathway T cell-specific kinase PKCθ. This mainly targets components translation such as mRNAs encoding ribosomal proteins eIF5A. Inducing eIF5A IES variant is by itself sufficient reduce global translation, consistently, observe reduced synthesis after cell activation. suggest ensuing decrease in efficiency help coordinate extensive changes expression during Together, these findings set a paradigm for alternative activation, provide evidence its functional relevance T-cell stimulation.

Язык: Английский

Процитировано

0
Overexpression of hnRNPK and inhibition of cytoplasmic translocation ameliorate lipid disorders in doxorubicin cardiotoxicity via PINK1/Parkin-mediated mitophagy DOI Creative Commons
Qian Xu, Xuehua Wang, Jing Hu

и другие.

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Lipid metabolism has been identified as a potential target for the treatment of doxorubicin-induced cardiomyopathy (DIC). Mitochondria, central regulator energy production and utilization, plays crucial role in this process, enhancing mitophagy holds promise mitigating myocardial damage DIC. However, relationship between lipid remains unclear, key molecules mediating connection remain to be elucidated. Among these candidates, heterogeneous nuclear ribonucleoprotein K (hnRNPK) emerges metabolism. its specific DIC unclear. In study, we established chronic models both vivo vitro assess hnRNPK levels, mitophagy, metabolism, well evaluate impact on cardiac function. Our findings revealed that expression is significantly reduced hearts cardiomyocytes doxorubicin (DOX)-treated mice. Notably, overexpression improves function effectively reduces accumulation by mitophagy. Mechanistically, was found downregulated DIC, accompanied translocation from nucleus cytoplasm, thereby reducing transcriptional regulation PINK1. Overexpression inhibition cytoplasmic alleviates DOX-induced regulating PINK1/Parkin pathway. These underscore previously unrecognized inhibiting prevent

Язык: Английский

Процитировано

0
irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA DOI
Luca Ducoli,

Brian Zarnegar,

Douglas F. Porter

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Язык: Английский

Процитировано

0
RNA-Binding Proteins in Cardiomyopathies DOI Creative Commons

De‐Li Shi

Journal of Cardiovascular Development and Disease, Год журнала: 2024, Номер 11(3), С. 88 - 88

Опубликована: Март 5, 2024

The post-transcriptional regulation of gene expression plays an important role in heart development and disease. Cardiac-specific alternative splicing, mediated by RNA-binding proteins, orchestrates the isoform switching proteins that are essential for cardiomyocyte organization contraction. Dysfunctions impair cause main types cardiomyopathies, which represent a heterogenous group abnormalities severely affect structure function. In particular, mutations RBM20 RBFOX2 associated with dilated cardiomyopathy, hypertrophic or hypoplastic left syndrome. Functional analyses different animal models also suggest possible roles other cardiomyopathies because their involvement organizing cardiac programming. Recent studies have provided significant insights into causal relationship between cardiovascular diseases. They show potential correcting pathogenic to rescue cardiomyopathy promote regeneration. Therefore, emerged as promising targets therapeutic interventions dysfunction. challenge remains decipher how they coordinately regulate temporal spatial target genes ensure function homeostasis. This review discusses recent advances understanding implications several well-characterized aim identifying research gaps further investigation this field.

Язык: Английский

Процитировано

3