α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts

α‐2‐Macroglobulin positively regulates microvesicle shedding through the activation of low‐density lipoprotein receptor‐related protein‐1 on myofibroblasts. AbstractMicrovesicles (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) responsib le 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 stimula tion 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.

Source: Journal of Cellular Physiology - November 27, 2018 Category: Cytology Authors: Alexandra Laberge, Akram Ayoub, Syrine Arif, S ébastien Larochelle, Alain Garnier, Véronique J. Moulin Tags: ORIGINAL RESEARCH ARTICLE Source Type: research