New role of alpha-2-macroglobulin into the shedding of microvesicles

Background: Cells release membranous structures known as microvesicles (MVs) that play an important role in tissue morphogenesis and wound healing. Myofibroblasts are cells present in healing tissue that produce new extracellular matrix, stimulate angiogenesis and contract wound edges. They have bee...

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Published inJournal of extracellular vesicles Vol. 7; p. 218
Main Authors Laberge, Alexandra, Ayoub, Akram, Arif, Syrine, Larochelle, Sebastien, Garnier, Alain, Moulin, Veronique J
Format Journal Article
LanguageEnglish
Published Abingdon John Wiley & Sons, Inc 01.01.2018
Subjects
Angiogenesis
Extracellular matrix
Mass spectroscopy
Morphogenesis
Receptor density
Wound healing
α2-Macroglobulin
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Summary:Background: Cells release membranous structures known as microvesicles (MVs) that play an important role in tissue morphogenesis and wound healing. Myofibroblasts are cells present in healing tissue that produce new extracellular matrix, stimulate angiogenesis and contract wound edges. They have been shown to shed MVs upon stimulation with serum or plasma. However, the exact molecule that induces MV production is unknown. Methods: A succession of chromatography, electrophoresis and mass spectrometry methods was performed on serum to identify the molecule that stimulates MV formation. Production of MVs by myofibroblasts was measured after each step of the purification sequence and after stimulation with two potent molecules. Results: Among the numerous proteins present in serum, alpha-2macroglobulin (A2M) was found to stimulate the production of MVs in a dose-dependent manner. We showed that low-density lipoprotein receptor-related protein 1 (LRP1), an A2M receptor, is expressed on the surface of myofibroblasts. Addition of inhibitors of A2M-LRP1 binding decreased the production of MVs by myofibroblasts. Summary/Conclusion: Stimulation of the shedding of MVs from myofibroblasts during wound healing is a novel function of A2M.
ISSN:2001-3078