Epithelial-Mesenchymal Transition, TGF-beta, 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: 1.55). 05/2012; 33(3):311-8. DOI: 10.1097/BCR.0b013e318240541e
Source: PubMed

ABSTRACT 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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    • "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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    ABSTRACT: Bladder cancer stem cell research is rapidly expanding based on the knowledge of cancer stem cells from various cancer types and normal stem cells as models. In various cancer types, cancer stem cells have been implicated in therapeutic resistance and relapse after initial therapy. Understanding how cancer stem cells differ from bulk cancer cells and how cancer stem cells contribute to relapse and resistance are essential to develop novel therapeutics to target cancer stem cells effectively. Here we review the latest information on bladder cancer stem cells, their biological characteristics, including their response to treatment, recurrence, immune context and technical problems encountered in bladder cancer stem cell research.
    Current Stem Cell Research & Therapy 11/2013; DOI:10.2174/1574888X08666131113123051 · 2.86 Impact Factor
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    • "Although considerable progress has been made towards understanding the etiology of the disease, the pathogenesis of pterygium is not completely understood (Bradley et al., 2008; Chui et al., 2008). EMT is critical in both developmental processes (Bolender and Markwald, 1979; Duband et al., 1995; Griffith and Hay, 1992; Viebahn, 1995), wound healing and tissue remodeling (Weber et al., 2012), and tumor metastasis (Thiery et al., 2009) and describes a reversible series of events during which epithelial cells lose cellecell contacts and acquire mesenchymal characteristics (Gregory et al., 2008b). These events involve molecular reprogramming of the cell, including loss or redistribution of epithelial-specific cellecell adhesion molecules such as E-cadherin, and turning on of mesenchymal markers including fibronectin, vimentin and N-cadherin (Thiery and Sleeman, 2006). "
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    ABSTRACT: The current study investigates whether microRNA (miRNA) regulators of epithelial-mesenchymal transition (EMT), tissue fibrosis, and angiogenesis are differentially expressed in human primary pterygium. Genome-wide miRNA and mRNA expression profiling of paired pterygium and normal conjunctiva was performed in the context of conventional excision of pterygium with autotransplantation of conjunctiva (n=8). Quantitative real time polymerase chain reaction (qRT-PCR) was used to validate the expression of key molecules previously detected by microarray. In pterygium, 25 miRNAs and 31 mRNAs were significantly differentially expressed by more than two-fold compared to normal conjunctiva. 14 miRNAs were up-regulated (miR-1246, -486, -451, -3172, -3175, -1308, -1972, -143, -211, -665, -1973, -18a, 143, and -663b), whereas 11 were down-regulated (miR-675, -200b-star, -200a-star, -29b, -200b, -210, -141, -31, -200a, -934, and -375). Unsupervised hierarchical cluster analysis demonstrated that members of the miR-200 family were coexpressed and down-regulated in pterygium. The molecular and cellular functions that were most significant to the miRNA data sets were cellular development, cellular growth and proliferation, and cellular movement. qRT-PCR confirmed the expression of 15 of the 16 genes tested and revealed that miR-429 was down-regulated by more than two-fold in pterygium. The concerted down-regulation of four members from both clusters of the miR-200 family (miR-200a/-200b/-429 and miR-200c/-141), which are known to regulate EMT, and up-regulation of the predicted target and mesenchymal marker fibronectin (FN1), suggest that EMT could potentially play a role in the pathogenesis of pterygium and might constitute promising new targets for therapeutic intervention in pterygium.
    Experimental Eye Research 07/2013; 115. DOI:10.1016/j.exer.2013.07.003 · 3.02 Impact Factor
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is involved in normal developmental cellular processes, but it may also be co-opted by a subset of cancer cells, to enable them to invade and form metastases at distant sites. Several gene transcription factors regulate EMT, including Snail1, Snail2, Zeb1, Zeb2, and Twist; ongoing studies continue to identify and elucidate other drivers. Specific micro ribonucleic acids (RNAs) have also been found to regulate EMT, including the microRNA-200 (miR-200) family, which targets Zeb1/Zeb2. Cancer "stem cells" - with the ability to self-renew and to regenerate all the cell types within the tumor - have been found to express EMT markers, further implicating both cancer stem cells and EMT with metastasis. Microenvironmental cues, including transforming growth factor-β, can direct EMT tumor metastasis, such as by regulating miR-200 expression. In human tumors, EMT markers and regulators may be expressed in a subset of tumor cells, such as in cells at the invasive front or tumor-microenvironment interface, though certain subtypes of cancer can show widespread mesenchymal-like features. In terms of therapeutic targeting of EMT in patients, potential areas of exploration could include targeting the cancer stem cell subpopulation, as well as microRNA-based therapeutics that reintroduce miR-200. This review will examine evidence for a role of EMT in invasion and metastasis, with the focus being on studies in lung and breast cancers. We also carry out analyses of publicly-available gene expression profiling datasets in order to show how EMT-associated genes appear coordinately expressed across human tumor specimens.
    Cancer Management and Research 07/2013; 5:187-95. DOI:10.2147/CMAR.S35171
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