Epithelial-Mesenchymal Transition, TGF-β, and Osteopontin in Wound Healing and Tissue Remodeling After Injury

Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Journal of burn care & research: official publication of the American Burn Association (Impact Factor: 1.43). 05/2012; 33(3):311-8. DOI: 10.1097/BCR.0b013e318240541e
Source: PubMed


Epithelial-mesenchymal transition (EMT) is a process essential to wound healing and tissue remodeling after a thermal burn or other injury. EMT is characterized by phenotypic changes in epithelial cells that render them apolar, with decreased cell-cell adhesions, increased motility, and changes in cytoskeletal architecture similar to mesenchymal stem cells. With regard to healing a thermal burn wound, many facets of wound healing necessitate cells to undergo these phenotypic changes; two will be described in the following review. The first is the differentiation of epithelial cells into myofibroblasts that rebuild the extracellular matrix and facilitate wound contraction. The second is reepithelialization by keratinocytes. The primary cytokine signal identified in the literature that triggers EMT is transforming growth factor (TGF)-β. In addition to its vital role in the induction of EMT, TGF-β has many other roles in the wound healing process. The following review will provide evidence that EMT is a central event in wound healing. It will also show the importance of a regulated amount of TGF-β for proper wound healing. Finally, osteopontin will be briefly discussed with its relation to wound healing and its connections to EMT and TGF-β.

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    • "The cellular origins are partially resolved: (i) Endothelial cells, required for the formation of new capillaries, can be derived from endothelial cells of the original blood vessels but also from the circulating endothelial progenitors (Potente et al. 2011). (ii) Fibroblasts can be derived from the connective tissue in the wound edges, from monocyte-derived fibrocytes (Grieb et al. 2011, Reilkoff et al. 2011), from vessel-derived pericytes (Grieb et al. 2011) and possibly also by a process termed epithelialmesenchymal transition (Weber et al. 2012). (iii) Epithelial cells originate from the keratinocytes at the wound edges, but at least in the skin, stem cells of the hair follicle can contribute to the re-epithelialization (Blanpain & Fuchs 2009, Cordeiro & Jacinto 2013). "
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    Journal Of Clinical Periodontology 04/2014; 41 Suppl s15(s15):S6-S22. DOI:10.1111/jcpe.12206 · 4.01 Impact Factor
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    • "This hypothesis is based on the fact that key mesenchymal markers, such as vimentin, fibronectin, N-Cadherin, alphavbeta3-integrins and FSP-1, can be detected in a subset of cancer cells. The EMT seems to pathologically recapitulate the normal epithelial-mesenchymal transition occurring during mammalian development, and is thought to be to some extent comparable to the EMT during physiological wound healing 3. However, there is some incongruity in this hypothesis, as it cannot explain why cancer cells with mesenchymal markers show many specifically phenotypical and functional traits of monocytes, macrophages, platelets and pre-/osteoclasts, i.e. traits of the myeloid lineage cells 4-11. "
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    ABSTRACT: Cancer cells express epithelial markers, and when progressing in malignancy they may express markers of the mesenchymal cell type. Therefore an epithelial-mesenchymal transition of the cancer cells is assumed. However the mesenchymal markers can equally well be interpreted as myeloid markers since they are common in both types of cell lineages. Moreover, cancer cells express multiple specific markers of the myeloid lineages thus giving rise to the hypothesis that the transition of cancer cells may be from epithelial to myeloid cells and not to mesenchymal cells. This interpretation would better explain why cancer cells, often already in their primary cancer site, frequently show properties common to those of macrophages, platelets and pre-/osteoclasts.
    Journal of Cancer 01/2014; 5(2):125-132. DOI:10.7150/jca.8242 · 3.27 Impact Factor
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    • "While many reasons could exist, one possibility is that the TURBT procedure (essentially causing a wound) could result in wound healing process with inflammatory and resolution phases (which are much similar to delayed hypersensitivity reaction), and which might give advantages to CSCs to escape from subsequent treatment. Furthermore, wound healing is a process that involves extensive epithelial to mesenchymal transition (EMT) [101], a phenotype linked to stemness and CSCs in recent years [102] and raising the possibility that the TURBT procedure may allow bladder CSC phenotype at least in some cells. The well-known field effect (formation of satellite tumors outside the area of resected primary tumor foci) observed in bladder cancer after TURBT may well be the after effect of EMT induction by wound healing and stemness induction. "
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