Mobility Tuning of Polyrotaxane Surfaces to Stimulate Myocyte Differentiation

Communication between the extracellular matrix and the intracellular signal transduction and cytoskeletal system is mediated by integrin receptors. α5β1-Integrin and its cognate ligand fibronectin are essential in development of mesodermal structures, myocyte differentiation, and normal cardiac development. To begin to explore the potential roles of α5β1-integrin specifically in cardiomyocytes, we used a transgenic expression strategy. We overexpressed two forms of the human α5-integrin in cardiomyocytes: the full-length wild-type α5-integrin and a putative gain-of-function mutation created by truncating the cytoplasmic domain, designated α5-1-integrin. Overexpression of the wild-type α5-integrin has no detectable adverse effects in the mouse, whereas expression of α5-1-integrin caused electrocardiographic abnormalities, fibrotic changes in the ventricle, and perinatal lethality. Thus physiological regulation of integrin function appears essential for maintenance of normal cardiomyocyte structure and function. This strengthens the role of inside-out signaling in regulation of integrins in vivo and suggests that integrins and associated signaling molecules are important in cardiomyocyte function.

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C2C12 cell culture model for investigating Ca 2+ ‐dependence of myocyte differentiation

The FASEB Journal ◽

10.1096/fasebj.25.1_supplement.lb598 ◽

2011 ◽

Vol 25 (S1) ◽

Author(s):

Brittany Jacobs ◽

Dapeng Chen ◽

Eva R Chin

Keyword(s):

Cell Culture ◽

C2c12 Cell ◽

Cell Culture Model ◽

Culture Model ◽

Myocyte Differentiation

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Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00050.2015 ◽

2015 ◽

Vol 309 (1) ◽

pp. L37-L45 ◽

Cited By ~ 9

Author(s):

Mylène Chevigny ◽

Karine Guérin-Montpetit ◽

Amandine Vargas ◽

Josiane Lefebvre-Lavoie ◽

Jean-Pierre Lavoie

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Serum Response Factor ◽

Smooth Muscles ◽

Peripheral Airways ◽

Myocyte Differentiation ◽

Antigenic Exposure ◽

Serum Response ◽

Muscle Remodeling

Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, a spontaneously occurring asthma-like disease of horses, and in controls. Six horses with heaves and five aged-matched controls kept in the same environment were studied. Nuclear protein expression of SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial biopsies obtained during disease remission and after 1 and 30 days of naturally occurring antigenic exposure using immunohistochemistry and immunofluorescence techniques. Nuclear expression of SRF ( P = 0.03, remission vs. 30 days) and MYOCD ( P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of horses with heaves during disease exacerbation, while MYOCD ( P = 0.04, remission vs. 30 days) decreased in the central airways of control horses. No changes were observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM observed in equine asthmatic airways, while the remodeling of the central airways is more static or involves different transcription factors.

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MicroRNA-1 transfected embryonic stem cells enhance cardiac myocyte differentiation and inhibit apoptosis by modulating the PTEN/Akt pathway in the infarcted heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00271.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. H2038-H2049 ◽

Cited By ~ 79

Author(s):

Carley Glass ◽

Dinender K. Singla

Keyword(s):

Cell Differentiation ◽

Cardiac Myocyte ◽

Heart Function ◽

Es Cells ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Border Zone ◽

Es Cell ◽

Infarcted Heart ◽

Myocyte Differentiation

microRNAs (miRs) have emerged as critical modulators of various physiological processes including stem cell differentiation. Indeed, miR-1 has been reported to play an integral role in the regulation of cardiac muscle progenitor cell differentiation. However, whether overexpression of miR-1 in embryonic stem (ES) cells (miR-1-ES cells) will enhance cardiac myocyte differentiation following transplantation into the infarcted myocardium is unknown. In the present study, myocardial infarction (MI) was produced in C57BL/6 mice by left anterior descending artery ligation. miR-1-ES cells, ES cells, or culture medium (control) was transplanted into the border zone of the infarcted heart, and 2 wk post-MI, cardiac myocyte differentiation, adverse ventricular remodeling, and cardiac function were assessed. We provide evidence demonstrating enhanced cardiac myocyte commitment of transplanted miR-1-ES cells in the mouse infarcted heart as compared with ES cells. Assessment of apoptosis revealed that overexpression of miR-1 in transplanted ES cells protected host myocardium from MI-induced apoptosis through activation of p-AKT and inhibition of caspase-3, phosphatase and tensin homolog, and superoxide production. A significant reduction in interstitial and vascular fibrosis was quantified in miR-1-ES cell and ES cell transplanted groups compared with control MI. However, no statistical significance between miR-1-ES cell and ES cell groups was observed. Finally, mice receiving miR-1-ES cell transplantation post-MI had significantly improved heart function compared with respective controls ( P < 0.05). Our data suggest miR-1 drives cardiac myocyte differentiation from transplanted ES cells and inhibits apoptosis post-MI, ultimately giving rise to enhanced cardiac repair, regeneration, and function.

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Notch1 regulates the fate of cardiac progenitor cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0808357105 ◽

2008 ◽

Vol 105 (40) ◽

pp. 15529-15534 ◽

Cited By ~ 148

Author(s):

Alessandro Boni ◽

Konrad Urbanek ◽

Angelo Nascimbene ◽

Toru Hosoda ◽

Hanqiao Zheng ◽

...

Keyword(s):

Progenitor Cells ◽

Cell Fate ◽

Nuclear Translocation ◽

Notch Receptor ◽

Cardiac Progenitor Cells ◽

Supporting Cells ◽

Multiple Organs ◽

Myocyte Differentiation ◽

Fate Decision

The Notch receptor mediates cell fate decision in multiple organs. In the current work we tested the hypothesis that Nkx2.5 is a target gene of Notch1 and raised the possibility that Notch1 regulates myocyte commitment in the adult heart. Cardiac progenitor cells (CPCs) in the niches express Notch1 receptor, and the supporting cells exhibit the Notch ligand Jagged1. The nuclear translocation of Notch1 intracellular domain (N1ICD) up-regulates Nkx2.5 in CPCs and promotes the formation of cycling myocytes in vitro. N1ICD and RBP-Jk form a protein complex, which in turn binds to the Nkx2.5 promoter initiating transcription and myocyte differentiation. In contrast, transcription factors of vascular cells are down-regulated by Jagged1 activation of the Notch1 pathway. Importantly, inhibition of Notch1 in infarcted mice impairs the commitment of resident CPCs to the myocyte lineage opposing cardiomyogenesis. These observations indicate that Notch1 favors the early specification of CPCs to the myocyte phenotype but maintains the newly formed cells in a highly proliferative state. Dividing Nkx2.5-positive myocytes correspond to transit amplifying cells, which condition the replicative capacity of the heart. In conclusion, Notch1 may have critical implications in the control of heart homeostasis and its adaptation to pathologic states.

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Analysis of Cripto expression during mouse cardiac myocyte differentiation

The International Journal of Developmental Biology ◽

10.1387/ijdb.130072jd ◽

2013 ◽

Vol 57 (9-10) ◽

pp. 793-797

Author(s):

Jiu-Zhen Jin ◽

Min Tan ◽

Jixiang Ding

Keyword(s):

Cardiac Myocyte ◽

Myocyte Differentiation

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Pharmacological priming of adipose-derived stem cells promotes myocardial repair

Journal of Investigative Medicine ◽

10.1136/jim-2015-000018 ◽

2016 ◽

Vol 64 (1) ◽

pp. 50-62 ◽

Cited By ~ 6

Author(s):

Jana S Burchfield ◽

Ashley L Paul ◽

Vishy Lanka ◽

Wei Tan ◽

Yongli Kong ◽

...

Keyword(s):

Stem Cells ◽

Cardiac Function ◽

Functional Recovery ◽

Cardiac Myocyte ◽

Left Ventricular ◽

Adipose Derived Stem Cells ◽

Myocardial Repair ◽

Myocyte Differentiation

Adipose-derived stem cells (ADSCs) have myocardial regeneration potential, and transplantation of these cells following myocardial infarction (MI) in animal models leads to modest improvements in cardiac function. We hypothesized that pharmacological priming of pre-transplanted ADSCs would further improve left ventricular functional recovery after MI. We previously identified a compound from a family of 3,5-disubstituted isoxazoles, ISX1, capable of activating an Nkx2-5-driven promoter construct. Here, using ADSCs, we found that ISX1 (20 mM, 4 days) triggered a robust, dose-dependent, fourfold increase in Nkx2-5 expression, an early marker of cardiac myocyte differentiation and increased ADSC viability in vitro. Co-culturing neonatal cardiomyocytes with ISX1-treated ADSCs increased early and late cardiac gene expression. Whereas ISX1 promoted ADSC differentiation toward a cardiogenic lineage, it did not elicit their complete differentiation or their differentiation into mature adipocytes, osteoblasts, or chondrocytes, suggesting that re-programming is cardiomyocyte specific. Cardiac transplantation of ADSCs improved left ventricular functional recovery following MI, a response which was significantly augmented by transplantation of ISX1- pretreated cells. Moreover, ISX1-treated and transplanted ADSCs engrafted and were detectable in the myocardium 3 weeks following MI, albeit at relatively small numbers. ISX1 treatment increased histone acetyltransferase (HAT) activity in ADSCs, which was associated with histone 3 and histone 4 acetylation. Finally, hearts transplanted with ISX1-treated ADSCs manifested significant increases in neovascularization, which may account for the improved cardiac function. These findings suggest that a strategy of drug-facilitated initiation of myocyte differentiation enhances exogenously transplanted ADSC persistence in vivo, and consequent tissue neovascularization, to improve cardiac function.

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