1. α-2-Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts.
- Author
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Laberge A, Ayoub A, Arif S, Larochelle S, Garnier A, and Moulin VJ
- Subjects
- Adult, Cell Communication physiology, Cells, Cultured, Extracellular Matrix metabolism, Healthy Volunteers, Humans, Low Density Lipoprotein Receptor-Related Protein-1 antagonists & inhibitors, Skin injuries, Young Adult, Cell-Derived Microparticles physiology, Low Density Lipoprotein Receptor-Related Protein-1 metabolism, Myofibroblasts physiology, Pregnancy-Associated alpha 2-Macroglobulins metabolism, Wound Healing physiology
- Abstract
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., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2019
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