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Exosomal miR-222-3p derived from dermal papilla cells inhibits melanogenesis in melanocytes by targeting SOX10 in rabbits |
Yang Chen1 
, Tingting Lu1
, Yingying Dai1
, Yu Xue1
, Bohao Zhao1
, Xinsheng Wu1,*
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College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China |
Correspondence:
Xinsheng Wu, Tel: +86-514-87997194, Fax: +86-514-87997194, Email: xswu@yzu.edu.cn
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Received: 26 March 2024 • Revised: 23 May 2024 • Accepted: 16 August 2024 |
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| Abstract |
Objective
Dermal papilla cells (DPCs) play a pivotal role in hair follicle development and can modulate melanogenesis in melanocytes (MCs) through their microenvironment. Our previous studies have demonstrated that the levels of exosomal miR-222-3p derived from DPCs of white Rex rabbits are significantly higher than those of black Rex rabbits. However, the specific role and underlying molecular mechanisms of exosomal miR-222-3p in melanogenesis remain elusive.
Methods
DPCs and MCs were isolated from hair follicles of Rex rabbits and identified using western blotting (WB) and immunofluorescent staining. Exosomes derived from DPCs (DPCs-exos) were characterized using nanoparticle tracking analysis, transmission electron microscopy, and WB. To investigate cell-cell crosstalk mediated by exosomes, MCs were co-cultured with CM-Dil-labeled DPCs-exos. The expression of miR-222-3p in skin tissue and exosomes was quantitatively assessed using quantitative real-time polymerase chain reaction. The transmission of DPCs-secreted exosomal miR-222-3p to MCs was demonstrated using Cy3-labeled miR-222-3p in conjunction with transwell assays. The impact of miR-222-3p on melanin synthesis was evaluated using the NaOH method, cell counting kit-8, and annexin V-fluorescein isothiocyanate/propidium iodide assays. Sex determining region Y-box 10 (SOX10), a potential target gene regulated by miR-222-3p, was validated using a dual-luciferase reporter assay, site-specific mutation, and WB.
Results
Increased levels of miR-222-3p were observed in the skin and DPCs-exos of white Rex rabbits compared to those of black Rex rabbits. Effective internalization of CM-Dillabeled DPCs-exos by MCs was observed. Furthermore, exosomal miR-222-3p derived from DPCs was transferred to MCs. Functionally, miR-222-3p significantly inhibited MCs proliferation, induced apoptosis and inhibited melanin synthesis. SOX10 was confirmed as a direct target of miR-222-3p in this regulatory cascade.
Conclusion
The findings demonstrate that exosomal miR-222-3p, derived from DPCs, suppresses melanogenesis in MCs by targeting SOX10, thus unveiling a novel mechanism of exosome involvement in melanogenesis. |
| Keywords:
Dermal Papilla Cells; Exosome; Melanocytes; Melanogenesis; miR-222-3p |
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