Abstract
Apoptosis is a universal and continuous event during tissue development, restoration, repair, and regeneration. Mounting evidence has demonstrated that apoptosis is essential for the activation of tissue regeneration. However, the underlying mechanism remains elusive. A striking development in recent years comes from research on extracellular vesicles (EVs) derived from apoptotic cells. During apoptosis, cells secrete vesicles of various sizes containing various components. Apoptotic cell-derived EVs (ApoEVs) have been found to transit to neighboring cells or cells in distant tissues through the circulation. These vesicles could act as containers to transmit the nucleic acid, protein, and lipid signals to target cells. ApoEVs have been shown to promote regeneration in the cardiovascular system, skin, bone, muscle, kidney, etc. Moreover, several specific signaling pathways mediating the anabolic effects of ApoEVs have been classified. In this review, we comprehensively discussed the latest findings on the function of ApoEVs in tissue regeneration and disease prevention. These findings may reveal unexpected clues regarding the regulatory network between cell death and tissue regeneration and suggest novel targets for regenerative medicine. The findings discussed here also raise the question whether and to what extent ApoEVs contribute to embryonic development. This question is all the more urgent because the exact functions of apoptotic events during numerous developmental processes are still largely unclear.
Highlights
Apoptosis refers to the spontaneous and orderly cell death and is controlled by a cluster of genes to maintain homeostasis (Kroemer et al, 2005)
Regeneration and embryonic development are partly based on common regulatory gene networks which, in both cases, may drive similar or even identical apoptosis and/or senescence processes
apoptotic cell-derived extracellular vesicles (ApoEVs) can transit to the target cells and exchange signaling molecules, including DNA, RNA, and proteins, to regulate cell proliferation and differentiation and tissue regeneration after phagocytosis
Summary
Apoptosis refers to the spontaneous and orderly cell death and is controlled by a cluster of genes to maintain homeostasis (Kroemer et al, 2005). Contained in endothelial cell-derived ApoBDs can induce the proliferation and differentiation of human endothelial progenitor cells in vitro (Hristov et al, 2004). By shuttling microRNA-221/222, macrophage-derived ApoBDs promote the proliferation of lung epithelial cells (Zhu et al, 2017).
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