English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/165951
Título

Epithelial contribution to the profibrotic stiff microenvironment and myofibroblast population in lung fibrosis

AutorGabasa, Marta; Rodríguez-Pascual, Fernando ; Alcaraz, Jordi
Fecha de publicación11-oct-2017
CitaciónMolecular Biology of the Cell 28: 3741- 3755 (2017)
ResumenThe 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 (fibrosisfree) 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-β1, 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-β1 stimulation. Yet IPF myofibroblasts exhibited higher stiffness and expression of fibrillar collagens than control fibroblasts, concomitantly with enhanced FAKY397 activity. FAK inhibition was sufficient to decrease fibroblast stiffness and collagen expression, supporting that FAKY397 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 FAKY397 may rescue normal mechanobiology in IPF.
URIhttp://hdl.handle.net/10261/165951
Identificadoresdoi: 10.1091/mbc.E17-01-0026
issn: 1939-4586
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Rodríguez-PascualF_EpithelialContribution.pdf5,79 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.