2026-04-29T02:37:45Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/225342024-11-28T18:20:04Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16962col_20.500.12105_16967

00925njm 22002777a 4500 dc Molina-Molina, M author Machahua-Huamani, C author Vicens-Zygmunt, V author Llatjos, R author Escobar, I author Sala Llinàs, Ernest author Luburich-Hernaiz, P author Dorca, J author Montes-Worboys, A author 2018-04-27 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. Molina-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. 1471-2466 http://hdl.handle.net/20.500.13003/9339 https://hdl.handle.net/20.500.12105/22534 29703175 10.1186/s12890-018-0626-4 BMC Pulmonary Medicine 2-s2.0-85046122919 431579900001 L621918416 Pirfenidone Rapamycin Idiopathic pulmonary fibrosis Pulmonary fibrosis Cell migration Extracellular matrix proteins Epithelial-mesenchymal transition Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells