ABSTRACT
Idiopathic pulmonary fibrosis can be caused by different factors, including accumulation of pathological extracellular matrix (ECM) with abnormal composition, stiffness, and architecture in the lung tissue. We studied the effect of ECM produced by lung fibroblasts of healthy mice or mice with bleomycin-induced pulmonary fibrosis on the process of endothelialto- mesenchymal transition, one of the main sources of effector myofibroblasts in fibrosis progression. Despite stimulation of spontaneous and TGFß-1-induced differentiation of fibroblasts into myofibroblasts by fibrotic ECM, the appearance of α-SMA, the main marker of myofibroblasts, and its integration in stress fibrils in endotheliocytes were not observed under similar conditions. However, the expression of transcription factors SNAI1 and SNAI2/Slug and the production of components of fibrotic ECM (specific EDA-fibronectin splice form and collagen type I) were increased in endotheliocytes cultured on fibrotic ECM. Endothelium also demonstrated increased cell velocity in the models of directed cell migration. These data indicate activation of the intermediate state of the endothelial-to-mesenchymal transition in endotheliocytes upon contact with fibrotic, but not normal stromal matrix. In combination with the complex microenvironment that develops during fibrosis progression, it can lead to the replenishment of myofibroblasts pool from the resident endothelium.
Subject(s)
Epithelial-Mesenchymal Transition/physiology , Extracellular Matrix/physiology , Pulmonary Fibrosis/pathology , Animals , Cell Differentiation/drug effects , Cells, Cultured , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/metabolism , Decellularized Extracellular Matrix/pharmacology , Endothelial Cells/drug effects , Endothelial Cells/physiology , Epithelial-Mesenchymal Transition/drug effects , Extracellular Matrix/metabolism , Female , Fibroblasts/drug effects , Fibroblasts/pathology , Fibroblasts/physiology , Human Umbilical Vein Endothelial Cells , Humans , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Mice , Mice, Inbred C57BL , Myofibroblasts/drug effects , Myofibroblasts/physiology , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/physiopathology , Signal Transduction/drug effects , Signal Transduction/physiology , Tissue ScaffoldsABSTRACT
The study aims to assess the role of EU biomedical research infrastructures in the fight against the COVID-19 pandemic and to analyze their response to the challenges associated with the spread of the new pathogen. Materials and Methods: We analyzed the materials of the Seventh Framework Program for Research and Technological Development (FP7, 2007-2013) of the EU and the Eighth Framework Program "Horizon 2020" (FP8, 2014-2020), official reports of the European Strategic Forum on Research Infrastructures, expert reports, as well as documents of the European Commission, the COVID-19 Data Portal, and other relevant sources of information. Results: The analysis revealed that the mechanisms created within the united European research community provided for a flexible response to the emerging threat of COVID-19 as soon as January-May 2020. In particular, information channels were established to timely analyze the research results and coordinate the efforts in the fight against COVID-19. The biomedical infrastructures created in the EU and proved successful earlier have now been mobilized to search for ways of preventing and treating COVID-19. These mechanisms facilitated communication and data exchange between various research institutions and thus laid the ground for new achievements in this area. Conclusion: The decisions taken to combat the COVID-19 pandemic have convincingly illustrated that the EU research infrastructures, integrated into a united ecosystem, are highly adaptable and flexible, which allows to realign priorities in a short time and to create instruments that enable scientists to respond to new challenges.