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Extracellular vesicles released by melanocytes after UVA irradiation promote intercellular signaling via miR21
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.ORCID iD: 0000-0003-4075-159X
2020 (English)In: Pigment Cell & Melanoma Research, ISSN 1755-1471, E-ISSN 1755-148XArticle in journal (Refereed) Epub ahead of print
Abstract [en]

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-beta 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.

Place, publisher, year, edition, pages
WILEY , 2020.
Keywords [en]
extracellular vesicles; keratinocytes; melanocytes; miR21; ultraviolet
National Category
Biophysics
Identifiers
URN: urn:nbn:se:liu:diva-163632DOI: 10.1111/pcmr.12860ISI: 000508164600001PubMedID: 31909885OAI: oai:DiVA.org:liu-163632DiVA, id: diva2:1393814
Note

Funding Agencies|Hudfonden [2835]; Ostgotaregionens Cancer Foundation; Swedish Cancer SocietySwedish Cancer Society [CAN-2016-735]; Forskningsradet i Sydostra Sverige [FORSS-850571]; County Council of Ostergotland [LIO-792031]; Olle Engkvist Foundation

Available from: 2020-02-17 Created: 2020-02-17 Last updated: 2020-02-17

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Wäster, PetraEriksson, IdaVainikka, LindaÖllinger, Karin
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Division of Cell BiologyFaculty of Medicine and Health SciencesDepartment of Clinical Pathology and Clinical Genetics
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