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Re-enforcing hypoxia-induced polyploid cardiomyocytes enter cytokinesis through activation of ?-catenin.

ABSTRACT: Cardiomyocyte (CM) loss is a characteristic of various heart diseases, including ischaemic heart disease. Cardiac regeneration has been suggested as a promising strategy to address CM loss. Although many studies of regeneration have focused mainly on mononucleated or diploid CM, the limitations associated with the cytokinesis of polyploid and multinucleated CMs remain less well known. Here, we show that ?-catenin, a key regulator in heart development, can increase cytokinesis in polyploid multinucleated CMs. The activation of ?-catenin increases the expression of the cytokinesis-related factor epithelial cell transforming 2 (ECT2), which regulates the actomyosin ring and thus leads to the completion of cytokinesis in polyploid CMs. In addition, hypoxia can induce polyploid and multinucleated CMs by increasing factors related to the G1-S-anaphase of the cell cycle, but not those related to cytokinesis. Our study therefore reveals that the ?-catenin can promote the cytokinesis of polyploid multinucleated CMs via upregulation of ECT2. These findings suggest a potential field of polyploid CM research that may be exploitable for cardiac regeneration therapy.

SUBMITTER: Jiang YH

PROVIDER: S-EPMC6883062 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Re-enforcing hypoxia-induced polyploid cardiomyocytes enter cytokinesis through activation of β-catenin.

Jiang Yun-Han YH Zhu Yu Y Chen Sai S Wang Hai-Long HL Zhou Yang Y Tang Fu-Qin FQ Jian Zhao Z Xiao Ying-Bin YB

Scientific reports 20191128 1

Cardiomyocyte (CM) loss is a characteristic of various heart diseases, including ischaemic heart disease. Cardiac regeneration has been suggested as a promising strategy to address CM loss. Although many studies of regeneration have focused mainly on mononucleated or diploid CM, the limitations associated with the cytokinesis of polyploid and multinucleated CMs remain less well known. Here, we show that β-catenin, a key regulator in heart development, can increase cytokinesis in polyploid multin ...[more]

PMID: 31780774

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Project description:Hair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced (EF skin) by transgenic epidermal activation of beta-catenin. We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of beta-catenin signalling. In contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal beta-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis. We have isolated the following populations of cells from mouse back skin by flow cytometry: 1A) GFP+ WT neonatal dermal fibroblasts, 1B) ItgA6+ WT neonatal epidermal keratinocytes, 2A) GFP+ WT telogen dermal fibroblasts, 2B) ItgA6+ WT telogen epidermal keratinocytes, 3A) GFP+ D2 transient activation (anagen) dermal fibroblasts, 3B) ItgA6+ D2 transient activation (anagen) epidermal keratinocytes, 4A) GFP+ D2 sustained activation (ectopic follicles) dermal fibroblasts, 4B) ItgA6+ D2 sustained activation (ectopic follicles) epidermal keratinocytes

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Re-enforcing hypoxia-induced polyploid cardiomyocytes enter cytokinesis through activation of ?-catenin.

Publications

Re-enforcing hypoxia-induced polyploid cardiomyocytes enter cytokinesis through activation of β-catenin.

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