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Review
. 2019 Apr 18:10:388.
doi: 10.3389/fphar.2019.00388. eCollection 2019.

Therapeutic Targeting of Fibrotic Epithelial-Mesenchymal Transition-An Outstanding Challenge

Attila Fintha  1 , Ákos Gasparics  2 , László Rosivall  3 , Attila Sebe  3   4
Affiliations
Review

Therapeutic Targeting of Fibrotic Epithelial-Mesenchymal Transition-An Outstanding Challenge

Attila Fintha et al. Front Pharmacol. .

Abstract

Back in 1995, a landmark paper was published, which shaped the fibrosis literature for many years to come. During the characterization of a fibroblast-specific marker (FSP1) in the kidneys, an observation was made, which gave rise to the hypothesis that "fibroblasts in some cases arise from the local conversion of epithelium." In the following years, epithelial-mesenchymal transition was in the spotlight of fibrosis research, especially in the kidney. However, the hypothesis came under scrutiny following some discouraging findings from lineage tracing experiments and clinical observations. In this review, we provide a timely overview of the current position of the epithelial-mesenchymal transition hypothesis in the context of fibrosis (with a certain focus on renal fibrosis) and highlight some of the potential hurdles and pitfalls preventing therapeutic breakthroughs targeting fibrotic epithelial-mesenchymal transition.

Keywords: chronic injury; epithelial to mesenchymal transition; fibrosis; myofibroblast; repair.

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Figures

Figure 1
Figure 1
The role of epithelial-mesenchymal plasticity during renal tubular repair and fibrosis. Upon acute kidney injury tubular regeneration takes place through tubular dedifferentiation and redifferentiation on the ground of a balanced epithelial-mesenchymal-epithelial cycle. Upon persistent, repeated injury the dedifferentiation process is hijacked and tubular epithelial cells support scarring via partial and complete EMT.
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