Molina-Molina, MMachahua-Huamani, CVicens-Zygmunt, VLlatjos, REscobar, ISala Llinàs, ErnestLuburich-Hernaiz, PDorca, JMontes-Worboys, A2024-09-062024-09-062018-04-27Molina-Molina M, Machahua-Huamani C, Vicens-Zygmunt V, Llatjos R, Escobar I, Sala-Llinas E, et al. Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells. BMC Pulm Med. 2018 Apr 27;18:63.1471-2466http://hdl.handle.net/20.500.13003/9339https://hdl.handle.net/20.500.12105/22534Background: 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.enghttp://creativecommons.org/licenses/by/4.0/PirfenidoneRapamycinIdiopathic pulmonary fibrosisPulmonary fibrosisCell migrationExtracellular matrix proteinsEpithelial-mesenchymal transitionAlveolar Epithelial CellsBiomarkersExtracellular MatrixEpithelial-Mesenchymal TransitionIdiopathic Pulmonary FibrosisMyofibroblastsPyridonesCell MovementHumansTransforming Growth Factor beta1A549 CellsSirolimusresearch articleAttribution 4.0 International29703175186310.1186/s12890-018-0626-4BMC Pulmonary Medicineopen accessFactor de Crecimiento Transformador beta1Movimiento CelularHumanosBiomarcadoresMiofibroblastosCélulas Epiteliales AlveolaresTransición Epitelial-MesenquimalSirolimusMatriz ExtracelularFibrosis Pulmonar IdiopáticaCélulas A549Piridonas2-s2.0-85046122919431579900001L621918416