Open AccessExosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up‐regulation of lysyl oxidase‐like 2
Author(s) -
Jong Olivier G.,
Balkom Bas W. M.,
Gremmels Hendrik,
Verhaar Marianne C.
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12730
Subject(s) - lysyl oxidase , microvesicles , exosome , extracellular matrix , microbiology and biotechnology , biology , matrix metalloproteinase , biochemistry , microrna , gene
Exosomes are important mediators of intercellular communication. Additionally, they contain a variety of components capable of interacting with the extracellular matrix ( ECM ), including integrins, matrix metalloproteinases and members of the immunoglobin superfamily. Despite these observations, research on exosome‐ECM interactions is limited. Here, we investigate whether the exosome‐associated lysyl oxidase family member lysyl oxidase‐like 2 ( LOXL 2) is involved in ECM remodelling. We found that LOXL 2 is present on the exterior of endothelial cell ( EC )‐derived exosomes, placing it in direct vicinity of the ECM . It is up‐regulated twofold in EC ‐derived exosomes cultured under hypoxic conditions. Intact exosomes from hypoxic EC and LOXL 2 overexpressing EC show increased activity in a fluorometric lysyl oxidase enzymatic activity assay as well as in a collagen gel contraction assay. Concordantly, knockdown of LOXL 2 in exosome‐producing EC in both normal and hypoxic conditions reduces activity of exosomes in both assays. Our findings show for the first time that ECM crosslinking by EC ‐derived exosomes is mediated by LOXL 2 under the regulation of hypoxia, and implicate a role for exosomes in hypoxia‐regulated focal ECM remodelling, a key process in both fibrosis and wound healing.