Abstract
The epithelial–mesenchymal transition (EMT) is an essential event during cell development, in which epithelial cells acquire mesenchymal fibroblast-like features including reduced intercellular adhesion and increased motility. EMT also plays a key role in wound healing processes, which are mediated by inflammatory cells and fibroblasts. These cells secrete specific factors that interact with molecules of the extracellular matrix (ECM) such as collagens, laminins, elastin and tenascins. Wound healing follows four distinct and successive phases characterized by haemostasis, inflammation, cell proliferation and finally tissue remodeling. EMT is classified into three diverse subtypes: type-1 EMT, type-2 EMT and type-3 EMT. Type-1 EMT is involved in embryogenesis and organ development. Type-2 EMT is associated with wound healing, tissue regeneration and organ fibrosis. During organ fibrosis, type-2 EMT occurs as a reparative-associated process in response to ongoing inflammation and eventually leads to organ destruction. Type-3 EMT is implicated in cancer progression, which is linked to the occurrence of genetic and epigenetic alterations, in detail the ones promoting clonal outgrowth and the formation of localized tumors. The current review aimed at exploring the role of EMT process with particular focus on type-2 EMT in wound healing, fibrosis and tissue regeneration, as well as some recent progresses in the EMT and tissue regeneration field, including the modulation of EMT by biomaterials.
Highlights
The epithelial–mesenchymal transition (EMT) is a pivotal process that plays a key role in physiological and pathological events, such as embryogenesis, wound healing and cancer development [1]
This EMT is required for the production of mesenchymal cells that are capable of successively undergoing a mesenchymal–epithelial transition (MET) to create secondary epithelia
The EMTs associated with wound healing, tissue regeneration and organ fibrosis are classified as type-2 EMTs
Summary
The epithelial–mesenchymal transition (EMT) is a pivotal process that plays a key role in physiological and pathological events, such as embryogenesis, wound healing and cancer development [1]. Type-1 EMT is associated with embryo implantation and development, as well as multiple organ formation, neither provokes fibrosis nor induces an invasive phenotype This EMT is required for the production of mesenchymal cells (primary mesenchyme) that are capable of successively undergoing a MET to create secondary epithelia. The EMTs associated with wound healing, tissue regeneration and organ fibrosis are classified as type-2 EMTs. Type-2 EMT events occur as part of a repair-associated process where the epithelial cells differentiate into novel fibroblast-like cells in order to rebuild tissues following trauma and inflammatory damage. The migratory cancer cells produced by type-3 EMT promote secondary tumours in distant tissues with epithelial phenotypes This suggests that the reversibility of EMT, which is a crucial factor in embryogenesis, plays a key role in the development of secondary metastatic nodules [13]. We described the EMT programs during physiological and pathological processes focusing in particular on the role played by type-2 EMT in wound healing, fibrosis and tissue regeneration, as well as some latests advancements in the EMT and tissue regeneration field including the modulation of EMT by biomaterials
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