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.

Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis

“…Myofibroblastic differentiation is a process that produces terminally differentiated myofibroblasts and is involved in tissue healing [ 150 ]. Myofibroblasts accumulate interstitial ECM components such as collagens and fibronectin during wound healing, and express abundant amounts of smooth muscle α-actin (α-SMA) [ 151 , 152 ]. These cells are ultimately incorporated into stress fibers [ 152 ].…”

Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial–Mesenchymal Transition

“…During organ fibrosis, type 2 EMT has been indicated as a mechanism responsible for reparative-associated processes in response to ongoing inflammation and oxidative stress [ 48 ]. A classic marker for EMT is change in cellular morphology [ 49 ] and cell motility [ 50 ], with increased expression of mesenchymal markers and decreased expression of epithelial proteins.…”

Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight Into the Roles of Transcription Factors

“…FIGURE 1 | The metastatic cascade. Epithelial tumours may sometimes undergo EMT to generate mesenchymal cells with more motile and invasive properties that penetrate the basal lamina (invasion [1]) and enter the bloodstream or lymphatic system, becoming circulating tumour cells (intravasation [2]), which are transported via the systemic circulation (circulation [3]), migrate into distant tissues that have the favourable cellular cues (extravasation [4]). The microenvironmental signals then induce an EMT reversal (also called MET) to establish secondary micrometastases (colonization [5]).…”

“…This type begins with the initial step of a repairassociated process that generates fibroblasts to regenerate tissue due to trauma and inflammatory damage. In contrast to type 1, type 2 does not continue indefinitely; it stops once the inflammatory process is attenuated (1,2). In organ fibrosis, however, the EMT process has a propensity for persistent response to recurring inflammatory reactions with the possibility of leading to organ damage.…”

“…As the knowledge of EMT roles in various tissue/organ development surges, three types of EMT have been recognised to occur in biological systems. Each type occurs in response to different biological signals and with different functional consequences ( 1 ).…”