Epithelial-Mesenchymal Transition (EMT): The Type-2 EMT in Wound Healing, Tissue Regeneration and Organ Fibrosis

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.