Premium
Extracellular vesicles released by melanocytes after UVA irradiation promote intercellular signaling via miR21
Author(s) -
Wäster Petra,
Eriksson Ida,
Vainikka Linda,
Öllinger Karin
Publication year - 2020
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12860
Subject(s) - microbiology and biotechnology , crosstalk , downregulation and upregulation , intracellular , signal transduction , extracellular , exosome , mapk/erk pathway , keratinocyte , chemistry , melanoma , exocytosis , apoptosis , biology , cancer research , microvesicles , microrna , secretion , biochemistry , in vitro , physics , optics , gene
Skin pigmentation is controlled by complex crosstalk between melanocytes and keratinocytes and is primarily induced by exposure to ultraviolet (UV) irradiation. Several aspects of UVA‐induced signaling remain to be explored. In skin cells, UVA induces plasma membrane damage, which is repaired by lysosomal exocytosis followed by instant shedding of extracellular vesicles (EVs) from the plasma membrane. The released EVs are taken up by neighboring cells. To elucidate the intercellular crosstalk induced by UVA irradiation, EVs were purified from UVA‐exposed melanocytes and added to keratinocytes. Transcriptome analysis of the keratinocytes revealed the activation of TGF‐β and IL‐6/STAT3 signaling pathways and subsequent upregulation of microRNA (miR)21. EVs induced phosphorylation of ERK and JNK, reduced protein levels of PDCD4 and PTEN, and augment antiapoptotic signaling. Consequently, keratinocyte proliferation and migration were stimulated and UV‐induced apoptosis was significantly reduced. Interestingly, melanoma cells and melanoma spheroids also generate increased amounts of EVs with capacity to stimulate proliferation and migration upon UVA. In conclusion, we present a novel intercellular crosstalk mediated by UVA‐induced lysosome‐derived EVs leading to the activation of proliferation and antiapoptotic signaling via miR21.