Tlatelpa Romero, BeatrizVázquez de Lara Cisneros, Luis G.Cañadas Benito, OlgaBlanco Rivero, AmayaOlmeda Lozano, BárbaraPérez Gil, JesúsMendoza Milla, CriseldaMartinez Vaquero, José LuisRomero, YairContreras Cruz, David Atahualpade la Rosa Paredes, RenéRuiz Salgado, SinuhéBerra Romani, RobertoCollantes Gutiérrez, Alonso AntonioPérez Fernández, María SusanaHernández Linares, María GuadalupeGuerrero Luna, Gabriel2025-09-242025-09-242025-07Tlatelpa-Romero, B.; Vázquez-de-Lara Cisneros, L.G.; Cañadas, O.; Blanco-Rivero, A.; Olmeda, B.; Pérez-Gil, J.; Mendoza-Milla, C.; Martinez-Vaquero, J.L.; Romero, Y.; Contreras-Cruz, D.A.; et al. Modulation of Pulmonary Fibrosis by Pulmonary Surfactant-Associated Phosphatidylethanolamine In Vitro and In Vivo. Int. J. Mol. Sci. 2025, 26, 7132. https://doi.org/10.3390/ijms261571321661-659610.3390/ijms26157132https://hdl.handle.net/20.500.14352/124300Funding: Part of this work was funded by the Spanish Ministry of Science and Innovation (grant PID2021-124932OB-I00 to O.C., B.O., A.B.-R. and J.P.-G.).Pulmonary fibrosis (PF) is characterized by excessive collagen deposition and impaired lung function. Pulmonary surfactant may modulate fibroblast activity and offer therapeutic benefits. We developed a natural porcine pulmonary surfactant (NPPS) enriched with 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine (PE) and evaluated its biophysical and biological properties. Biophysical analysis showed that PE improved surfactant performance by increasing surface pressure and stability. In vitro, NPPS-PE reduced collagen expression and induced apoptosis in normal human lung fibroblasts; in addition, it decreased proliferation in fibroblasts stimulated with TGF-β. In vivo, NPPS-PE improved gas exchange and significantly reduced collagen deposition in bleomycin-treated mice. These findings suggest that NPPS-PE may be a promising therapeutic strategy for fibrosing lung diseases.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1422-0067https://doi.org/10.3390/ijms26157132https://www.mdpi.com/1422-0067/26/15/7132open access577.115616.2615.015Native porcine pulmonary surfactantPhosphatidylethanolamineSurface tensionBiophysical evaluationLung lavagesPulmonary fibrosisBioquímica (Biología)FisiologíaFarmacología (Medicina)2403 Bioquímica2411.17 Fisiología de la Respiración3209.90 Farmacología Experimental