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Epithelial-mesenchymal transition in tissue repair and fibrosis

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Abstract

The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-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 plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are 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 faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues.

Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right)

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Authors and Affiliations

  1. Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1600 NW 10th Avenue, RMSB, Room 2023A, Miami, FL 33136, USA

    Rivka C. Stone, Irena Pastar, Nkemcho Ojeh, Vivien Chen, Sophia Liu, Karen I. Garzon & Marjana Tomic-Canic

  2. The Research Residency Program, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Fla., USA

    Rivka C. Stone

  3. Faculty of Medical Sciences, The University of the West Indies, Bridgetown, Barbados

    Nkemcho Ojeh

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  1. Rivka C. Stone
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  2. Irena Pastar
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  3. Nkemcho Ojeh
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Correspondence to Marjana Tomic-Canic.

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Our research is supported by the National Institutes of Health grants NR015649, NR013881, and DK098055.

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Stone, R.C., Pastar, I., Ojeh, N. et al. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res 365, 495–506 (2016). https://doi.org/10.1007/s00441-016-2464-0

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