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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/123933
Anti-fibrotic Effects Of Pirfenidone And Rapamycin In Primary Ipf Fibroblasts And Human Alveolar Epithelial Cells
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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.
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MOLINA MOLINA, María, MACHAHUA, Carlos, VICENS ZYGMUNT, Vanesa, LLATJÓS, Roger, ESCOBAR, I., SALA LLINÀS, Ernest, LUBURICH HERNAIZ, Patricio, DORCA I SARGATAL, Jordi, MONTES WORBOYS, Ana. Anti-fibrotic Effects Of Pirfenidone And Rapamycin In Primary Ipf Fibroblasts And Human Alveolar Epithelial Cells. _Bmc Pulmonary Medicine_. 2018. Vol. 18:63. [consulta: 21 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/123933]