Abstract
Recent advances in our understanding of the molecular pathways that control the link of inflammation with organ fibrosis and autoimmune diseases point to the epithelial to mesenchymal transition (EMT) as the common association in the progression of these diseases characterized by an intense inflammatory response. EMT, a process in which epithelial cells are gradually transformed to mesenchymal cells, is a major contributor to the pathogenesis of fibrosis. Importantly, the chronic inflammatory microenvironment has emerged as a decisive factor in the induction of pathological EMT. Transforming growth factor-β (TGF-β), a multifunctional cytokine, plays a crucial role in the induction of fibrosis, often associated with chronic phases of inflammatory diseases, contributing to marked fibrotic changes that severely impair normal tissue architecture and function. The understanding of molecular mechanisms underlying EMT-dependent fibrosis has both a basic and a translational relevance, since it may be useful to design therapies aimed at counteracting organ deterioration and failure. To this end, we reviewed the recent literature to better elucidate the molecular response to inflammatory/fibrogenic signals in autoimmune diseases in order to further the specific regulation of EMT-dependent fibrosis in more targeted therapies.
Highlights
In view of the large volume of data present in the literature, this review is focused on the latest news about the relevance of the transforming growth factor (TGF)-β signalling pathway in the regulation of epithelial cell plasticity during the pathogenesis and progression of chronic inflammatory diseases characterized by intense pathological fibrosis, as well as on the ability of Transforming growth factor-β (TGF-β) to promote Epithelial–mesenchymal transition (EMT)-induced fibrosis in several autoimmune conditions
transglutaminase 2 (TG2) was shown to play a key role in invadosome formation by fibroblast-like synoviocytes (RA-FLS), through its ability to cross-link with the extracellular matrix (ECM) and to determine the activation of TGF-β [152]
There is strong evidence of the EMT role in fibrosis, associated to chronic inflammatory conditions and autoimmunity but further observations will be needed to determine whether a full trans-differentiation of epithelial cells to myofibroblasts does really occur in vivo
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The concept that organ failure triggers the inflammatory wound healing cascade, and that pathologically persistent inflammation is closely associated with severe fibrosis, was recently linked to atrophy and fibrosis of the salivary glands (SGs) [17,33,34,35] It occurs after several episodes of inflammatory states following chronic infections in the glands, as in primary Sjögren’s syndrome (pSS) a progressive systemic autoimmune disease [17,25,35]. In view of the large volume of data present in the literature, this review is focused on the latest news about the relevance of the transforming growth factor (TGF)-β signalling pathway in the regulation of epithelial cell plasticity during the pathogenesis and progression of chronic inflammatory diseases characterized by intense pathological fibrosis, as well as on the ability of TGF-β to promote EMT-induced fibrosis in several autoimmune conditions
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