Extracellular vesicles released by melanocytes after UVA irradiation promote intercellular signaling via miR21
Autor: | Petra Wäster, Ida Eriksson, Karin Öllinger, Linda Vainikka |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
MAPK/ERK pathway Keratinocytes Ultraviolet Rays Down-Regulation Apoptosis Dermatology Models Biological General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Extracellular Vesicles 0302 clinical medicine Downregulation and upregulation Cell Movement medicine Humans Gene Regulatory Networks Melanoma Cell Proliferation Chemistry Infant Newborn Infant medicine.disease Cell biology Up-Regulation Crosstalk (biology) MicroRNAs 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Child Preschool Phosphorylation Melanocytes sense organs Keratinocyte Extracellular Space Transcriptome Intracellular Signal Transduction |
Zdroj: | Pigment cellmelanoma researchREFERENCES. 33(4) |
ISSN: | 1755-148X |
Popis: | 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. |
Databáze: | OpenAIRE |
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