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.

中文翻译：

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UVA照射后黑素细胞释放的细胞外囊泡通过miR21促进细胞间信号传导。

皮肤色素沉着是由黑素细胞和角质形成细胞之间复杂的串扰控制的，并且主要是由暴露于紫外线（UV）照射引起的。UVA诱导的信号传导的几个方面仍有待探索。在皮肤细胞中，UVA诱导质膜损伤，其通过溶酶体胞吐作用修复，随后细胞质囊泡（EVs）立即从质膜脱落。释放的EV被相邻的电池占用。为了阐明由UVA照射引起的细胞间串扰，从暴露于UVA的黑素细胞中纯化EV，并将其添加到角质形成细胞中。角质形成细胞的转录组分析揭示了TGF-β和IL-6 / STAT3信号通路的激活以及随后的microRNA（miR）21上调。电动汽车诱导ERK和JNK磷酸化，降低PDCD4和PTEN的蛋白质水平，并增强抗凋亡信号。因此，刺激了角质形成细胞的增殖和迁移，并显着减少了紫外线诱导的细胞凋亡。有趣的是，黑色素瘤细胞和黑色素瘤球体也产生增加量的EV，具有刺激UVA增殖和迁移的能力。总之，我们提出了一种由UVA诱导的溶酶体来源的EV介导的新型细胞间串扰，可通过miR21激活增殖和抗凋亡信号。