title: Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.
abstract: Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma.
authors: Bioscience Research Division, R&D Unit, AmorePacific Corporation, Yongin, Republic of Korea.
authors: Bum-Ho
authors: BH
authors: Bin
authors: Department of Life Sciences, POSTECH, Pohang, Republic of Korea.
authors: Dae-Kyum
authors: DK
authors: Kim
authors: Department of Dermatology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
authors: Nan-Hyung
authors: NH
authors: Kim
authors: Bioscience Research Division, R&D Unit, AmorePacific Corporation, Yongin, Republic of Korea.
authors: Eun-Jeong
authors: EJ
authors: Choi
authors: Department of Chemical Engineering, POSTECH, Pohang, Republic of Korea.
authors: Jinhyuk
authors: J
authors: Bhin
authors: Bioscience Research Division, R&D Unit, AmorePacific Corporation, Yongin, Republic of Korea.
authors: Sung Tae
authors: ST
authors: Kim
authors: Department of Life Sciences, POSTECH, Pohang, Republic of Korea.
authors: Yong Song
authors: YS
authors: Gho
authors: Department of Dermatology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
authors: Ai-Young
authors: AY
authors: Lee
authors: Bioscience Research Division, R&D Unit, AmorePacific Corporation, Yongin, Republic of Korea. Electronic address: TRLee@amorepacific.com.
authors: Tae Ryong
authors: TR
authors: Lee
authors: Bioscience Research Division, R&D Unit, AmorePacific Corporation, Yongin, Republic of Korea. Electronic address: egcho@amorepacific.com.
authors: Eun-Gyung
authors: EG
authors: Cho
mesh_terms: D001707:Biopsy, Needle; D015153:Blotting, Western; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000528:radiation effects; D005353:Fibronectins / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D008548:Melanosis / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D012016:Reference Values; D012494:Sampling Studies; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D005353:Fibronectins