Editorial: Molecular mechanisms and new therapeutic targets in epithelial to mesenchymal transition (EMT) and fibrosis, volume II

The induction of inflammatory epithelial-mesenchymal transition (EMT)/fibrosis requires a complex cellular reprogramming process involving epithelial, stromal, and immune cells and has important implications on cell survival, plasticity, and migratory/invasive abilities. A wide array of extracellular stimuli, including soluble mediators, cell-to-cell interactions, and binding to the extracellular matrix (ECM), drive changes in resident cells towards a mesenchymal-like/profibrotic phenotype. The classical EMT/fibrosis pathways induced by transforming growth factor (TGF)-β, the central profibrotic mediator, as well as by tumor necrosis factor (TNF)α and epidermal growth factor (EGF) are well known. Here we focused on the roles of new intracellular mechanisms involved in the modulation of EMT/fibrosis. Moreover, a better understanding of the crosstalk between classical EMT/fibrosis pathways and stress signaling pathways, such as autophagy and unfolded protein response (UPR) become increasingly important in the field. Epigenetic processes, including histone acetylation and DNA/histone methylation, were shown to be essential modulators of the persistence of a new mesenchymal-like state or the reversion to an epithelial-like phenotype. Recent single-cell RNA-sequencing (scRNA-seq) experiments revealed that EMT transition is a transcriptional continuum of numerous epithelial-mesenchymal states rather than a binary epithelial vs. mesenchymal model. These recent insights considerably enhanced the understanding of the complexity and cell-specificity of this essential physio-pathological process. However, despite considerable efforts in the field, new mechanisms remain to be elucidated, and cell-type specificities have yet to be fully characterized. In this Research Topic, Sara Lovisa provided an updated overview of the recent debate on the definition of EMT, analyzing the impact of new technologies such as single cell transcriptomics. Moreover, the author summarized the different strategies used to define EMT in fibrotic disorders.