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Published on: June 7, 2019
miR-25-5p in exosomes derived from UVB-induced fibroblasts regulates melanogenesis via TSC2-dominated cellular
Hedan Yang1, Xiaoli Zhang1, Wenzhu Wang1
1Department of Cosmetic Laser Surgery, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
Background:
Few reports have confirmed whether exosomes derived from fibroblasts can regulate the process of melanogenesis. We wondered whether exosomes derived from fibroblasts could have a potent regulatory effect on melanogenesis and explored the underlying mechanisms.
Objective:
This study aimed to find the role of fibroblasts in melanocytes and revealed the related mechanisms.
Methods:
RT-qPCR, Western blot analysis were conducted to measure the RNA and protein expression level of various related genes. miRNA sequencing, mass spectrum analysis and subsequent bioinformatics analysis were employed to find the underlying targets. Zebrafish were employed to measure the melanin synthesis related process in vivo. Furthermore, electron microscopy, ROS measurement and dual-luciferase reporter assay were adopted to investigate the relationship between these processes.
Results:
We found that exosomes derived from human primary dermal fibroblasts were internalized by human primary melanocytes and MNT1 cells and that the melanin content and the expression of melanin synthesis-related proteins TYR and MITF was inhibited by exosomes derived from UVB-induced human primary dermal fibroblasts. The miRNA expression profile in secreted exosomes changed significantly, with miR-25-5p identified as capable of regulating TSC2 expression via the CDS region. The miR-25-5p-TSC2 axis could affect the melanin content through subsequent cellular organelle dysfunction, such as mitochondrial dysfunction, endoplasmic reticulum stress and dysregulation of lysosomal cysteine proteases.
Conclusion:
We unveiled a novel regulatory role of fibroblasts in melanocytes, facilitated by the secretion of exosomes. miR-25-5p within exosomes plays a pivotal role in regulating melanogenesis via TSC2-induced cellular organelle dysfunction.
Insights
Fibroblast exosomes inhibit melanogenesis by delivering miR-25-5p, which targets TSC2, leading to cellular organelle dysfunction. This reveals a novel fibroblast role in regulating skin pigmentation via exosome-mediated mechanisms.
Area of Science:
- Cell Biology
- Dermatology
- Molecular Biology
Background:
- Limited understanding exists regarding the role of fibroblast-derived exosomes in regulating melanogenesis.
- This study investigates the potential of fibroblast exosomes to influence melanin production and explores the underlying molecular mechanisms.
Purpose of the Study:
- To elucidate the role of fibroblasts in melanocyte function through exosome-mediated communication.
- To identify the specific molecular pathways and mechanisms involved in fibroblast regulation of melanogenesis.
Main Methods:
- Utilized RT-qPCR and Western blot to analyze gene and protein expression.
- Performed miRNA sequencing, mass spectrometry, and bioinformatics analysis to identify exosomal cargo and targets.
- Employed zebrafish models, electron microscopy, ROS assays, and dual-luciferase reporter assays to validate findings in vivo and in vitro.
Main Results:
- Exosomes from UVB-induced fibroblasts inhibited melanin content and expression of TYR and MITF in melanocytes.
- miR-25-5p was identified in exosomes, regulating TSC2 expression and subsequently affecting melanin synthesis.
- The miR-25-5p-TSC2 pathway induced cellular organelle dysfunction, including mitochondrial issues, ER stress, and lysosomal protease dysregulation.
Conclusions:
- Fibroblasts regulate melanocytes via secreted exosomes, establishing a novel intercellular communication pathway.
- Exosomal miR-25-5p is a key regulator of melanogenesis, acting through the TSC2-mediated organelle dysfunction pathway.
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