LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration

Wu, Yahan; Zhou, Liping; Liu, Hongyu; Duan, Ran; Zhou, Huixing; Zhang, Fulei; He, Xiaoyu; Lu, Dongbo; Xiong, Kaixin; Xiong, Maolin; Zhuang, Jinzhu; Liu, Yi; Li, Li; Liang, Dandan; Chen, Yihan

doi:10.1038/s41422-020-00411-7

Cited by 50 publications

(39 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To achieve optimal parathyroid hormone (PTH) signalling activation, LRP6 may possibly act as a coreceptor for the PTH receptor [ 72 ]. Cardiomyocyte proliferation is regulated by LRP6 via the ING5/P21 pathway [ 73 ]. Therefore, further molecular and functional investigations are required to fully understand these possible LRP6 interactions, which must be taken into consideration when Lrp6 is targeted for a potential therapeutic purpose.…”

Section: Lrp6 As a Potential Therapeutic Targetmentioning

confidence: 99%

LRP6 Receptor Plays Essential Functions in Development and Human Diseases

Alrefaei

Abu‐Elmagd

2022

Genes

View full text Add to dashboard Cite

LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors. It is required for the activation of the Wnt/β-catenin signalling pathway. LRP6 is detected in different tissue types and is involved in numerous biological activities such as cell proliferation, specification, metastatic cancer, and embryonic development. LRP6 is essential for the proper development of different organs in vertebrates, such as Xenopus laevis, chickens, and mice. In human, LRP6 overexpression and mutations have been reported in multiple complex diseases including hypertension, atherosclerosis, and cancers. Clinical studies have shown that LRP6 is involved in various kinds of cancer, such as bladder and breast cancer. Therefore, in this review, we focus on the structure of LRP6 and its interactions with Wnt inhibitors (DKK1, SOST). We also discuss the expression of LRP6 in different model systems, with emphasis on its function in development and human diseases.

show abstract

Section: Lrp6 As a Potential Therapeutic Targetmentioning

confidence: 99%

LRP6 Receptor Plays Essential Functions in Development and Human Diseases

Alrefaei

Abu‐Elmagd

2022

Genes

View full text Add to dashboard Cite

show abstract

“…Intriguingly, the accumulation of β-catenin has been observed upon constitutive activation of ERBB2 signaling, specifically mediating cardiomyocyte dedifferentiation (102). Ablation of lipoprotein-related receptor protein LRP6 (a coreceptor interacting with Frizzled receptor in Wnt/β-catenin signaling) in infarcted mouse hearts stimulates robust regenerative processes through the proliferation of pre-existing cardiomyocytes via a β-catenin independent mechanism, involving ING5 (inhibitor of growth family member 5)/p21 (206).…”

Section: Signaling Cascadesmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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.

show abstract

“…Nuclei were determined as tetraploid if their intensity values were within 1.5-2.5 times range of the reference cells. Polyploidy was assigned if DAPI intensity was greater than 2.5 times range of reference cells, as previously described 53 .…”

Section: Ploidy and Nuclear Volume Measurementmentioning

confidence: 99%

Adult spiny mice (Acomys) exhibit endogenous cardiac recovery in response to myocardial infarction

et al. 2021

View full text Add to dashboard Cite

Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying distinct characteristics. In response to myocardial infarction, all animals experienced a comparable level of initial cardiac damage. However, Acomys demonstrated superior ischemic tolerance and cytoprotection in response to injury as evidenced by cardiac functional stabilization, higher survival rate, and smaller scar size 50 days after injury compared to the inbred and outbred mouse strains. This phenomenon correlated with enhanced endothelial cell proliferation, increased angiogenesis, and medium vessel maturation in the peri-infarct and infarct regions. Overall, these findings demonstrate augmented myocardial preservation in spiny mice post-MI and establish Acomys as a new adult mammalian model for cardiac research.

show abstract

LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration

Cited by 50 publications

References 66 publications

LRP6 Receptor Plays Essential Functions in Development and Human Diseases

LRP6 Receptor Plays Essential Functions in Development and Human Diseases

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

Adult spiny mice (Acomys) exhibit endogenous cardiac recovery in response to myocardial infarction

Contact Info

Product

Resources

About