Switching on EMT in the peritoneal membrane: considering the evidence

Epithelial-to-mesenchymal transition (EMT) in its simplest terms is a process by which cells that are not normally motile, i.e. epithelial cells, undergo morphological changes to become motile cells [1]. During embryonic development, EMT is a critically important process, with most adult tissues arising from a series of controlled epithelial-to-mesenchymal transitions [2]. In adult life, the inflammatory cytokine environment created during tissue injury can also drive myofibroblast formation by the same mechanism, and as such, EMT is a critical and helpful process in wound healing and tissue repair [3] [1]. While EMT plays these important ‘physiological roles’, it is now widely recognized that this transformation process has significant pathological implications. It has now been directly implicated in cancer progression and many fibrotic diseases [1,2]. A multitude of clinical studies have identified that epithelial cells in many different organs, e.g. renal tubules [4], lens epithelium [5], alveolar epithelial cells [6] and peritoneal mesothelial cells [7], appear to contribute significantly to tissue fibrosis by undergoing this transition to a myofibroblast and mature fibroblast phenotype. The major challenge impeding progress in this field has been the difficulty experienced in robustly determining that EMT has actually occurred. Fundamentally, detecting a change in cell phenotype or measuring movement of a cell is the only true way to establish EMT. These types of analysis, while feasible in vitro, are virtually impossible to detect in vivo particularly in humans where access to tissues at that particular stage of disease (where EMT is occurring) is rarely possible and ultra-structural identification of the process is open to interpretation. As a result, the vast majority of studies rely upon the detection of specific biomarkers that reflect a transition in the expression o