Endothelial Microparticles are Associated to Pathogenesis of Idiopathic Pulmonary Fibrosis
Autor: | Elisa Rossi, Séverine Lecourt, Nour Bacha, Dominique Israel-Biet, Pascale Gaussem, Nicolas Gendron, Jean Marie Renard, Chantal M. Boulanger, Nathalie Nevo, Eduardo Anglés-Cano, Coralie L. Guerin, David M. Smadja, Adeline Blandinières |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Cancer Research 030204 cardiovascular system & hematology Pathogenesis Endothelial activation 03 medical and health sciences Idiopathic pulmonary fibrosis 0302 clinical medicine Cell-Derived Microparticles DLCO Diffusing capacity Humans Medicine Progenitor cell Myofibroblasts Lung Cells Cultured Aged Endothelial Progenitor Cells Aged 80 and over business.industry Cell Differentiation Cell Biology Fibroblasts Middle Aged respiratory system Flow Cytometry medicine.disease Urokinase-Type Plasminogen Activator Healthy Volunteers Idiopathic Pulmonary Fibrosis respiratory tract diseases 030104 developmental biology medicine.anatomical_structure Cancer research Female Collagen business Myofibroblast |
Zdroj: | Stem Cell Reviews and Reports. 14:223-235 |
ISSN: | 1558-6804 1550-8943 |
Popis: | Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms remain unclear but involve a concomitant accumulation of scar tissue together with myofibroblasts activation. Microparticles (MPs) have been investigated in several human lung diseases as possible pathogenic elements, prognosis markers and therapeutic targets. We postulated that levels and cellular origins of circulating MPs might serve as biomarkers in IPF patients and/or as active players of fibrogenesis. Flow cytometry analysis showed a higher level of Annexin-V positive endothelial and platelet MPs in 41 IPF patients compared to 22 healthy volunteers. Moreover, in IPF patients with a low diffusing capacity of the lung for carbon monoxide (DLCO 40% (p = 0.02). We then used EMPs isolated from endothelial progenitor cells (ECFCs) extracted from IPF patients or controls to modulate normal human lung fibroblast (NHLF) properties. We showed that EMPs did not modify proliferation, collagen deposition and myofibroblast transdifferentiation. However, EMPs from IPF patients stimulated migration capacity of NHLF. We hypothesized that this effect could result from EMPs fibrinolytic properties and found indeed higher plasminogen activation potential in total circulating MPs and ECFCs derived MPs issued from IPF patients compared to those isolated from healthy controls MPs. Our study showed that IPF is associated with an increased level of EMPs in the most severe patients, highlighting an active process of endothelial activation in the latter. Endothelial microparticles might contribute to the lung fibroblast invasion mediated, at least in part, by a fibrinolytic activity. |
Databáze: | OpenAIRE |
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