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J Cell Physiol. 2019 Jul;234(7):11369-11379. doi: 10.1002/jcp.27794. Epub 2018 Nov 27.

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

Author information

1
Centre de Recherche en Organogenèse Expérimentale de l'Université Laval (LOEX), Quebec, QC, Canada.
2
Centre de Recherche du CHU de Quebec-Université Laval, Quebec, QC, Canada.
3
Department of Chemical Engineering, Faculty of Sciences and Engineering, Université Laval, Quebec, QC, Canada.
4
Department of Surgery, Faculty of Medicine, Université Laval, Quebec, QC, Canada.

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.

KEYWORDS:

cell-derived microparticles; low-density lipoprotein receptor-related protein-1; myofibroblasts; wound healing; α-macroglobulins

PMID:
30479021
DOI:
10.1002/jcp.27794

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