Exosomal miRNA derived from keratinocytes regulates pigmentation in melanocytes

Abstract

Background: Pigmentation is controlled by complex mechanisms. Evidence suggests that miRNAs can regulate pigmentation. However, the mechanism has not been fully elucidated. Objective In this study, we revealed a novel mechanism that regulates pigmentation involving exosomes, miRNAs and the crosstalk between keratinocytes and melanocytes. Methods: The expression and localization of exosome specific marker TSG101 in keratinocytes and melanocytes; Changes of melanin content in melanocytes after co-culture of exosome and melanocytes; Expression changes of target gene TYR and its related genes and inhibitory effect of miR-330-5p on pigmentation were studied by using various molecular biological techniques. Results: In this experiment, we used miR-330-5p in keratinocytes to verify the effect of keratinocyte derived exosome on melanocyte pigmentation. First, we found that keratinocytes secrete exosomes carrying miR-330-5p; moreover, greater miR-330-5p expression was found in exosomes derived from keratinocytes that overexpressed miR-330-5p. Second, we found that exosomes derived from keratinocytes with overexpression of miR-330-5p caused a significant increase in miR-330-5p in melanocytes. Finally, exosomes derived from keratinocytes that overexpressed miR-330-5p induced a significant decrease in the production of melanin and expression of TYR in melanocytes. Meanwhile, we overexpressed miR-330-5p in melanocytes, which also proved the inhibitory effect of miR-330-5p on pigmentation. Conclusion: These findings suggest that keratinocytes crosstalk with melanocytes in the epidermal melanin unit via exosomal miRNAs. These studies reveal an important role of exosomes in melanocyte pigmentation, which opens a new pathway of melanogenesis.

Quantitative changes in the secretion of exosomes from keratinocytes homeostatically regulate skin pigmentation in a paracrine manner

“…The pathway by which vesicles (exosomes) secreted into the extracellular space function as a means of intercellular communication has been attracting attention in recent years . This scientific concept has facilitated investigations of the transmission of information between keratinocytes and melanocytes and it was reported several years ago that normal human keratinocytes release exosomes that play a role in regulating pigmentation . That study reported that miRNA secreted within exosomes can target melanocytes, resulting in the modulation of their pigmented status by altering levels of gene expression and enzyme activity.…”

“…Interestingly, miR‐675 was detected in the media from keratinocyte cultures and was suggested to be possibly released from keratinocytes as one type of inclusion in exosomes, and to be involved in regulating melanogenesis by melanocytes through effects on microphthalmia‐associated transcription factor (MITF) as a target . In addition to miR‐675, the effect of miR‐330‐5p derived from the keratinocytes' exosome on melanocyte pigmentation was also verified recently . Furthermore, another study suggested that keratinocytes regulate melanocyte pigmentation by modulating their miRNA content in exosomes …”

“…20 In addition to miR-675, the effect of miR-330-5p derived from the keratinocytes' exosome on melanocyte pigmentation was also verified recently. 23 Furthermore, another study suggested that keratinocytes regulate melanocyte pigmentation by modulating their miRNA content in exosomes. 19 Despite greater attention as an intercellular communication tool in the epidermal melanin unit, those findings were derived from studies at the cellular level, and it remained to be determined whether those results reflect actual skin conditions in vivo.…”

Ultraviolet B irradiation enhances the secretion of exosomes by human primary melanocytes and changes their exosomal miRNA profile

“…Exosomes are common EVs originated form endosomes with a diameter of 30-150 nm [6,7], and they carry numerous biological substances, such as proteins, mRNAs, microRNAs (miRNAs), cytokines, and transcription factors [8]. Studies have shown that melanocytes are the target of exosomes secreted by other cells, such as keratinocytes [9][10][11]; as for exosomes derived from melanocytes, their role in other cells is rarely investigated. Solar radiation stimulates the synthesis of melanin in melanocytes and the transport of melanin-containing melanosomes to neighboring epidermal cells, resulting in skin pigmentation.…”

Down‐regulation of exosomal miR‐200c derived from keratinocytes in vitiligo lesions suppresses melanogenesis

“…17 However, some miRNAs from keratinocyte exosomes negatively regulate melanogenesis in melanocytes, such as miR-330-5p and miR-675. 20,21 In vitiligo, we investigated whether exosomes derived from keratinocytes still have the ability to modulate melanogenesis in melanocytes. Our study revealed that exosomes secreted by VLK have a weaker capacity for promoting melanogenesis of melanocytes.…”