GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro. - Université de Lille Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2021

GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro.

Résumé

The development of more effective, better tolerated drug treatments for progressive pulmonary fibrosis (of which idiopathic pulmonary fibrosis is the most common and severe form) is a research priority. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a key regulator of inflammation and fibrosis and therefore represents a potential therapeutic target. However, the use of synthetic PPAR-γ agonists may be limited by their potentially severe adverse effects. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, we have demonstrated that the non-racemic selective PPAR-γ modulator GED-0507 is able to reduce body weight loss, ameliorate clinical and histological features of pulmonary fibrosis, and increase survival rate without any safety concerns. Here, we focused on the biomolecular effects of GED-0507 on various inflammatory/fibrotic pathways. We demonstrated that preventive and therapeutic administration of GED-0507 reduced the BLM-induced mRNA expression of several markers of fibrosis, including transforming growth factor (TGF)-β, alpha-smooth muscle actin, collagen and fibronectin as well as epithelial-to-mesenchymal transition (EMT) and expression of mucin 5B. The beneficial effect of GED-0507 on pulmonary fibrosis was confirmed in vitro by its ability to control TGFβ-induced myofibroblast activation in the A549 human alveolar epithelial cell line, the MRC-5 lung fibroblast line, and primary human lung fibroblasts. Compared with the US Food and Drug Administration-approved antifibrotic drugs pirfenidone and nintedanib, GED-0507 displayed greater antifibrotic activity by controlling alveolar epithelial cell dysfunction, EMT, and extracellular matrix remodeling. In conclusion, GED-0507 demonstrated potent antifibrotic properties and might be a promising drug candidate for the treatment of pulmonary fibrosis.
Fichier principal
Vignette du fichier
journal.pone.0257281.pdf (3.54 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04482627 , version 1 (28-02-2024)

Licence

Paternité

Identifiants

Citer

Silvia Speca, Caroline Dubuquoy, Christel Rousseaux, Philippe Chavatte, Pierre Desreumaux, et al.. GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro.. PLoS ONE, 2021, PLoS ONE, 16, pp.e0257281. ⟨10.1371/journal.pone.0257281⟩. ⟨hal-04482627⟩

Collections

RIIP UNIV-LILLE
4 Consultations
1 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More