Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis.

European Respiratory Review : an Official Journal of the European Respiratory Society
Antoine FroidureArnaud Mailleux

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation of alveoli. Signals are then delivered to fibroblasts that undergo differentiation into myofibroblasts. These changes in lung architecture require the activation of developmental pathways that are important regulators of cell transformation, growth and migration. Among others, aberrant expression of profibrotic Wnt-β-catenin, transforming growth factor-β and Sonic hedgehog pathways in IPF fibroblasts has been assessed. In the present review, we will discuss the transcriptional integration of these different pathways during IPF as compared with lung early ontogeny. We will challenge the hypothesis that aberrant transcriptional integration of these pathways might be under the control of a chaotic dynamic, meaning that a small change in baseline conditions could be sufficient to trigger fibrosis rather than repair in a chronically injured lung. Finally, we will discuss some potential opportunities for treatment, either by suppressing d...Continue Reading

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Citations

Jul 13, 2021·Frontiers in Physiology·François M CarlierCharles Pilette
Nov 6, 2021·The European Respiratory Journal·Charles Fouillade, Arturo Londoño-Vallejo

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