In vitro and in vivo roles of glucocorticoid and vitamin D receptors in the control of neonatal cardiomyocyte proliferative potential

Cutie, Stephen; Payumo, Alexander Y.; Lunn, Dominic; Huang, Guo N.

doi:10.1016/j.yjmcc.2020.04.013

Cited by 18 publications

(24 citation statements)

References 47 publications

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“…In contrast, the administration of Vitamin D to cultured mouse cardiomyocytes has been reported to induce both anti-proliferative (168,(174)(175)(176) and pro-proliferative effects (173). Furthermore, the deletion of the Vitamin D receptor appears not sufficient to prolong the postnatal cardiomyocyte proliferative window in the mouse model (168). A potential explanation of these conflicting results could be that the effects of Vitamin D on cell proliferation may be context-dependent and/or concentration-dependent.…”

Section: Systemic Hormonesmentioning

confidence: 98%

“…Further analysis unveiled that GR ablation increases cardiomyocyte replication by regulating the energetic metabolism, favoring glucose catabolism over fatty acid oxidation [pre-publication by Pianca and colleagues (167)]. However, in later stages of postnatal life, no differences in cardiomyocyte proliferation rate were reported in GR ablated compared to control mice (168). Nevertheless, upon myocardial infarction, cardiomyocytes in GR ablated juvenile and adult mice are facilitated to re-enter into the cell cycle and divide, leading to regeneration of the lost cardiac tissue along with reduced scar formation [pre-publication by Pianca and colleagues (167)].…”

Section: Systemic Hormonesmentioning

confidence: 99%

“…In zebrafish, Vitamin D promotes cardiomyocyte cycling and tissue regeneration, and this process requires intact Erbb2 signaling (173). In contrast, the administration of Vitamin D to cultured mouse cardiomyocytes has been reported to induce both anti-proliferative (168,(174)(175)(176) and pro-proliferative effects (173). Furthermore, the deletion of the Vitamin D receptor appears not sufficient to prolong the postnatal cardiomyocyte proliferative window in the mouse model (168).…”

Section: Systemic Hormonesmentioning

confidence: 99%

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Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes

Bongiovanni

Sacchi

Pra

et al. 2021

Front. Cardiovasc. Med.

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Despite considerable efforts carried out to develop stem/progenitor cell-based technologies aiming at replacing and restoring the cardiac tissue following severe damages, thus far no strategies based on adult stem cell transplantation have been demonstrated to efficiently generate new cardiac muscle cells. Intriguingly, dedifferentiation, and proliferation of pre-existing cardiomyocytes and not stem cell differentiation represent the preponderant cellular mechanism by which lower vertebrates spontaneously regenerate the injured heart. Mammals can also regenerate their heart up to the early neonatal period, even in this case by activating the proliferation of endogenous cardiomyocytes. However, the mammalian cardiac regenerative potential is dramatically reduced soon after birth, when most cardiomyocytes exit from the cell cycle, undergo further maturation, and continue to grow in size. Although a slow rate of cardiomyocyte turnover has also been documented in adult mammals, both in mice and humans, this is not enough to sustain a robust regenerative process. Nevertheless, these remarkable findings opened the door to a branch of novel regenerative approaches aiming at reactivating the endogenous cardiac regenerative potential by triggering a partial dedifferentiation process and cell cycle re-entry in endogenous cardiomyocytes. Several adaptations from intrauterine to extrauterine life starting at birth and continuing in the immediate neonatal period concur to the loss of the mammalian cardiac regenerative ability. A wide range of systemic and microenvironmental factors or cell-intrinsic molecular players proved to regulate cardiomyocyte proliferation and their manipulation has been explored as a therapeutic strategy to boost cardiac function after injuries. We here review the scientific knowledge gained thus far in this novel and flourishing field of research, elucidating the key biological and molecular mechanisms whose modulation may represent a viable approach for regenerating the human damaged myocardium.

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Section: Systemic Hormonesmentioning

confidence: 98%

Section: Systemic Hormonesmentioning

confidence: 99%

Section: Systemic Hormonesmentioning

confidence: 99%

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Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes

Bongiovanni

Sacchi

Pra

et al. 2021

Front. Cardiovasc. Med.

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“…Meanwhile, in fetal mouse cardiomyocytes, two recent studies have demonstrated that the administration of corticosterone results in a decrease in cell proliferation in vitro and in vivo 78 . In addition, cytokinesis inhibition was observed in cardiomyocytes harvested from postnatal day 1 mice and grown in culture 78 , although it was not observed during a separate in vivo study at postnatal day 7 79 , a difference that may be attributed to differences in the ages of the mice or to different environmental signals. Meanwhile, prohibiting corticosterone signaling through cardiomyocyte-specific glucocorticoid receptor ablation results in increased cardiomyocyte proliferation and heart regeneration after myocardial infarction at postnatal day 7 78 , although this result was not replicated in a study that treated mice with a glucocorticoid receptor antagonist after myocardial infarction at postnatal day 1 79 .…”

Section: Internal Cuesmentioning

confidence: 94%

A cross-species analysis of systemic mediators of repair and complex tissue regeneration

2021

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Regeneration is an elegant and complex process informed by both local and long-range signals. Many current studies on regeneration are largely limited to investigations of local modulators within a canonical cohort of model organisms. Enhanced genetic tools increasingly enable precise temporal and spatial perturbations within these model regenerators, and these have primarily been applied to cells within the local injury site. Meanwhile, many aspects of broader spatial regulators of regeneration have not yet been examined with the same level of scrutiny. Recent studies have shed important insight into the significant effects of environmental cues and circulating factors on the regenerative process. These observations highlight that consideration of more systemic and possibly more broadly acting cues will also be critical to fully understand complex tissue regeneration. In this review, we explore the ways in which systemic cues and circulating factors affect the initiation of regeneration, the regenerative process, and its outcome. As this is a broad topic, we conceptually divide the factors based on their initial input as either external cues (for example, starvation and light/dark cycle) or internal cues (for example, hormones); however, all of these inputs ultimately lead to internal responses. We consider studies performed in a diverse set of organisms, including vertebrates and invertebrates. Through analysis of systemic mediators of regeneration, we argue that increased investigation of these “systemic factors” could reveal novel insights that may pave the way for a diverse set of therapeutic avenues.

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“…In this context, the hypothalamic-pituitary-adrenal axis plays a pivotal role during embryonic development with potent programming effects on organ development [222]. Recent studies support the role of glucocorticoids in regulating CM development [223][224][225][226]. In vitro studies report that thyroid and glucocorticoid hormones are critical for CMs maturation, also suggesting a method to improve PSC-CMs differentiation efficiency and maturity [224,225].…”

Section: Glucocorticoidsmentioning

confidence: 99%

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

Lamberto

Peral-Sanchez

Muenthaisong

et al. 2021

Genes

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Non-communicable diseases (NCDs) sauch as diabetes, obesity and cardiovascular diseases are rising rapidly in all countries world-wide. Environmental maternal factors (e.g., diet, oxidative stress, drugs and many others), maternal illnesses and other stressors can predispose the newborn to develop diseases during different stages of life. The connection between environmental factors and NCDs was formulated by David Barker and colleagues as the Developmental Origins of Health and Disease (DOHaD) hypothesis. In this review, we describe the DOHaD concept and the effects of several environmental stressors on the health of the progeny, providing both animal and human evidence. We focus on cardiovascular diseases which represent the leading cause of death worldwide. The purpose of this review is to discuss how in vitro studies with pluripotent stem cells (PSCs), such as embryonic and induced pluripotent stem cells (ESC, iPSC), can underpin the research on non-genetic heart conditions. The PSCs could provide a tool to recapitulate aspects of embryonic development “in a dish”, studying the effects of environmental exposure during cardiomyocyte (CM) differentiation and maturation, establishing a link to molecular mechanism and epigenetics.

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In vitro and in vivo roles of glucocorticoid and vitamin D receptors in the control of neonatal cardiomyocyte proliferative potential

Cited by 18 publications

References 47 publications

Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes

Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes

A cross-species analysis of systemic mediators of repair and complex tissue regeneration

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

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