Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells

Autor: Maria Molina-Molina, Roger Llatjós, Ignacio Escobar, P. Luburich-Hernaiz, Vanesa Vicens-Zygmunt, E. Sala-Llinas, Jordi Dorca, Ana Montes-Worboys, C. Machahua-Huamani
Rok vydání: 2018
Předmět:
0301 basic medicine
humanos
Pirfenidone
Idiopathic pulmonary fibrosis
0302 clinical medicine
Cell Movement
Pulmonary fibrosis
Myofibroblasts
biology
Fibrosi pulmonar
Extracellular matrix
Matriu extracel·lular
Extracellular Matrix
medicine.anatomical_structure
Extracellular matrix proteins
030220 oncology & carcinogenesis
fibrosis pulmonar idiopática
Myofibroblast
Research Article
medicine.drug
Pulmonary and Respiratory Medicine
Epithelial-Mesenchymal Transition
Pyridones
Therapeutics
matriz extracelular
Fibroblast migration
Transforming Growth Factor beta1
transición epiteliomesenquimatosa
03 medical and health sciences
medicine
Humans
Cell migration
Rapamycin
Fibroblast
Sirolimus
lcsh:RC705-779
A549 cell
business.industry
factor de crecimiento transformador beta1
miofibroblastos
lcsh:Diseases of the respiratory system
Terapèutica
medicine.disease
Fibronectin
030104 developmental biology
A549 Cells
Alveolar Epithelial Cells
movimiento celular
biology.protein
Cancer research
piridonas
business
Biomarkers
Zdroj: Recercat. Dipósit de la Recerca de Catalunya
instname
BMC Pulmonary Medicine, Vol 18, Iss 1, Pp 1-13 (2018)
BMC Pulmonary Medicine
Dipòsit Digital de la UB
Universidad de Barcelona
ISSN: 1471-2466
Popis: Background: Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. Methods: Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor beta 1 (TGF-beta). Extracellular matrix protein and gene expression of markers involved in lung fibrosis (tenascin-c, fibronectin, collagen I (COM Al], collagen III [COL3A1] and alpha-smooth muscle actin [alpha-SMA]) were analyzed. A cell migration assay in pirfenidone, rapamycin and TGF-beta-containing media was performed. Results: Gene and protein expression of tenascin-c and fibronectin of fibrotic fibroblasts were reduced by pirfenidone or rapamycin treatment Pirfenidone-rapamycin treatment did not revert the epithelial to mesenchymal transition pathway activated by TGF-beta. However, the drug combination significantly abrogated fibroblast to myofibroblast transition. The inhibitory effect of pirfenidone on fibroblast migration in the scratch-wound assay was potentiated by rapamycin combination. Conclusions: These findings indicate that the combination of pirfenidone and rapamycin widen the inhibition range of fibrogenic markers and prevents fibroblast migration. These results would open a new line of research for an anti-fibrotic combination therapeutic approach.
This study was supported by Proyectos de Investigacion en Salud del Instituto de Salud Carlos III (FIS PI 15/00710), Hoffmann-La Roche.
Databáze: OpenAIRE
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