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α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts
Author(s) -
Laberge Alexandra,
Ayoub Akram,
Arif Syrine,
Larochelle Sébastien,
Garnier Alain,
Moulin Véronique J.
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27794
Subject(s) - microvesicles , lrp1 , microbiology and biotechnology , myofibroblast , wound healing , stimulation , receptor , biogenesis , mediator , chemistry , endocytosis , scavenger receptor , biology , ldl receptor , biochemistry , immunology , lipoprotein , endocrinology , medicine , microrna , cholesterol , gene , fibrosis
Microvesicles (MVs) are recognized as an important class of cell‐to‐cell messengers. Although the properties of MVs are increasingly documented, the mechanisms regulating MV biogenesis remain debated. Myofibroblasts are a key cellular component of wound healing and have been shown to produce MVs upon stimulation with serum. However, the mediator(s) responsible for the observed effect of serum on MV release have yet to be identified. To isolate the molecule(s) of interest, serum proteins were sequentially separated using chromatography, selective precipitation, and electrophoresis. MV production was assessed throughout the purification and after stimulation of myofibroblasts with two potent purified molecules. α‐2‐Macroglobulin (A2M) was thereby found to dose‐dependently stimulate MV release. We confirmed the presence of the A2M receptor, low‐density lipoprotein receptor‐related protein‐1 (LRP1), on myofibroblasts. Inhibition of LRP1 resulted in a significant decrease in MV production. Together, our results suggest that A2M positively regulates MV shedding through the activation of LRP1 on myofibroblasts.