To access the full text documents, please follow this link: http://hdl.handle.net/2445/124162

Title:	Epithelial contribution to the profibrotic stiff microenvironment and myofibroblast population in lung fibrosis
Author:	Gabasa Ferràndez, Marta; Duch, Paula; Jorba, Ignasi; Giménez Hidalgo, Alicia; Lugo, Roberto; Pavelescu, Irina; Rodriguez Pascual, Fernando; Molina Molina, María; Xaubet Mir, Antonio; Pereda, Javier; Alcaraz Casademunt, Jordi
Notes:	The contribution of epithelial-to-mesenchymal transition (EMT) to the profibrotic stiff microenvironment and myofibroblast accumulation in pulmonary fibrosis remains unclear. We examined EMT-competent lung epithelial cells and lung fibroblasts from control (fibrosis-free) donors or patients with idiopathic pulmonary fibrosis (IPF), which is a very aggressive fibrotic disorder. Cells were cultured on profibrotic conditions including stiff substrata and TGF-beta 1, and analyzed in terms of morphology, stiffness, and expression of EMT/myofibroblast markers and fibrillar collagens. All fibroblasts acquired a robust myofibroblast phenotype on TGF-beta 1 stimulation. Yet IPF myofibroblasts exhibited higher stiffness and expression of fibrillar collagens than control fibroblasts, concomitantly with enhanced FAK(Y397) activity. FAK inhibition was sufficient to decrease fibroblast stiffness and collagen expression, supporting that FAK(Y397) hyperactivation may underlie the aberrant mechanobiology of IPF fibroblasts. In contrast, cells undergoing EMT failed to reach the values exhibited by IPF myofibroblasts in all parameters examined. Likewise, EMT could be distinguished from nonactivated control fibroblasts, suggesting that EMT does not elicit myofibroblast precursors either. Our data suggest that EMT does not contribute directly to the myofibroblast population, and may contribute to the stiff fibrotic microenvironment through their own stiffness but not their collagen expression. Our results also support that targeting FAK(Y397) may rescue normal mechanobiology in IPF.
Subject(s):	-Fibrosi pulmonar -Cèl·lules epitelials -Pulmonary fibrosis -Epithelial cells
Rights:	cc-by-nc-sa (c) Gabasa Ferràndez, Marta et al., 2017 http://creativecommons.org/licenses/by-nc-sa/3.0/es
Document type:	Article Article - Published version
Published by:	American Society for Cell Biology
Share:

Show full item record