0000000000309080
AUTHOR
Joëlle Marchal-somme
The small heat-shock protein α B-crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF-β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB-crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB-crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad-dependent pathway. We demonstrate here that αB-crystallin is stron…
Le FGF-9 inhibe la fibrose pleurale induite par un adénovirus chez la souris
La fibrose pulmonaire idiopathique (FPI) est une pathologie incurable et mortelle. Elle debute et predomine dans les regions sous-pleurales. Elle serait la consequence d’une reactivation des voies impliquees dans le developpement pulmonaire et d’une anomalie de communication entre les differentes cellules pulmonaires. Le fibroblast growth factor-9 (FGF-9) est necessaire pour le developpement pulmonaire fœtal. Au cours de la FPI, le FGF-9 est reexprime par les cellules mesotheliales pleurales. L’objectif de ce travail est de determiner l’effet de la surexpression de FGF-9 par les cellules mesotheliales de la plevre au cours du processus fibrosant pulmonaire. Materiel et methodes De souris mâ…
FGF-9 overexpression prevents pleural fibrosis induced by intra-pleural adenovirus injection in mice
Introduction: Lung fibrosis is associated with the reactivation of molecular pathways involved in lung development. Mesothelial cells are involved in the fibrotic lung process but their exact role is debated. Fibroblast Growth Factor-9 (FGF-9) is expressed by epithelial cells and visceral pleura during embryonic lung development. Mice homozygous for a targeted disruption of FGF-9 exhibit lung hypoplasia with reduced mesenchyme and early postnatal death. The aim of this study was to evaluate the role of FGF-9 expression by mesothelial cells in the adult lung. We used adenovirus-mediated (FGF-9) gene transfer in mesothelial cells in vivo. Material and Methods: AdFGF9 or a control adenovirus (…
Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation. Transition of epithelial/mesothelial cells into myofibroblasts [epithelial-to-mesenchymal transition (EMT)] occurs under the influence of transforming growth factor (TGF)-β1, with Snail being a major transcription factor. We study here the role of the heat-shock protein HSP27 in fibrogenesis and EMT. In vitro, we have up- and down-modulated HSP27 expression in mesothelial and epithelial cell lines and studied the expression of different EMT markers induced by TGF-β1. In vivo, we inhibited HSP27 with the antisense oligonucleotide OGX-427 (in phase II clinical trials as anticancer agent)…
Le FGF-9 inhibe la fibrose pleurale viro-induite chez la souris
La fibrose pulmonaire idiopathique (FPI) est une pathologie mortelle, predominante en zone sous-pleurale. Elle serait en partie due a une reactivation des voies impliquees dans le developpement pulmonaire. Le Fibroblast Growth Factor-9 (FGF-9) est reexprime par les cellules mesotheliales lors de la FPI. Nous avons determine l’effet de la surexpression de FGF-9 par les cellules mesotheliales chez la souris. Des souris C56/Bl6 ont recu une injection intrapleurale unique de serum physiologique (groupe Phy) ou un adenovirus recombine exprimant le FGF-9 humain (groupe AdFGF-9) ou un adenovirus controle (groupe Adcont), a la concentration de 1 × 108 pfu/mL. Les souris ont ete sacrifiees a j3, j5,…