Epithelial-mesenchymal transition in tissue repair and fibrosis

Abstract

Epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics which confer migratory capacity. EMT and its converse, MET (mesenchymal-to-epithelial transition), are integral stages of many physiologic processes, and as such are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes - the resident skin epithelial cells - migrate across the wound bed to restore the epidermal barrier. Moreover, EMT also plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblast arises from cells of epithelial lineage in response to injury but is pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the impaired repair of fibrotic wounds may identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues.

Skin Wound Healing: An Update on the Current Knowledge and Concepts

“…Other authors depicted leader cells or even entire cell rows that drag others with them to crawl over the wound [27,28,29,30]. Additionally, 3 other mechanisms might also be involved such as extension membrane or epidermal tongue, lamellipodial crawling and shuffling [31,32]. The epidermal tongue is formed by the front row of keratinocytes adjacent to the wound site.…”

Apple of Sodom (<em>Calatropis procera</em>) Callus Extract, a Novel Skincare Active and Its Biological Activity in Skin Models When Combined with Dead Sea Water

“…C. procera extract + DSW combination demonstrated also a significant induction in fibronectin enzyme expression. Of note, fibronectin participates in regeneration and healing process and might be related to EMT process [24]. Yet, treatment with C. procera extract as stand-alone also enhanced fibronectin expression.…”

“…Fibronectin is a key master of the extracellular matrix (ECM), forming essential connections between cell surface integrin receptors and structural components of the ECM, enhancing skin cells differentiation, assisting in regeneration and healing [24]. Figure 5(c) indicates that both topical treatment with C. procera extract alone and the mixture of C. procera extract and DSW extract were observed to significantly increase fibronectin production by 22% and 20%, respectively.…”

The Role of Epithelial-Mesenchymal Transition in Chronic Obstructive Pulmonary Disease

“…There are considered to be 3 types of EMT: types 1, 2, and 3 [Kalluri and Weinberg, 2009;Stone et al, 2016]. Type 1 EMT occurs during embryogenesis and the development of the fetus, giving rise to the mesenchymal ridge and allowing the epithelial embryonic cells to develop into mesenchymal structures Thiery et al, 2009].…”