RRC ID 72615
著者 Miyachi K, Yamada T, Sanada A, Inoue Y, Hasebe Y, Arima M, Iwata Y, Hasegawa S, Sugiura K, Akamatsu H.
タイトル Melanin accumulation in dermal stem cells deteriorates their exosome-mediated skin basement membrane construction in solar lentigo.
ジャーナル Exp Dermatol
Abstract Solar lentigo (SL) is a hyperpigmented macule that occurs in sun-exposed areas and is characterized by the accumulation of melanin pigment in the epidermis. On the contrary, melanin-incorporated macrophages have also been identified in the dermis, which is thought to be caused by melanin transfer due to disruption of the basement membrane, but the detailed mechanism remains unclear. In this study, we analysed SL lesions by pathological methods and examined the mechanism of melanin accumulation in the dermis using cultured skin models in vitro. First, we observed a significant decrease in type IV collagen (COL4), a major component of the basement membrane, in SL lesions. The basement membrane is known to be formed by the interaction of keratinocytes and dermal cells. Therefore, we constructed skin models containing fibroblasts or dermal stem cells and examined their effects on basement membrane formation. The results showed a markedly enhanced production of COL4 mediated by dermal stem cell-derived exosomes. The analysis of melanin localization in the SL dermis revealed that CD163-positive macrophages and CD271-positive dermal stem cells both took up melanin pigment. Exosomes of dermal stem cells incorporating melanosomes were less effective in promoting COL4 expression. These findings suggest that while the promotion of COL4 production in keratinocytes by dermal stem cell-derived exosomes is important for maintaining basement membrane homeostasis, this mechanism is disrupted in SL lesions, leading to chronic melanin accumulation in the dermis.
巻・号 31(12)
ページ 1881-1890
公開日 2022-12-1
DOI 10.1111/exd.14667
PMID 36048560
MeSH Basement Membrane / metabolism Collagen Type IV Dermis / metabolism Epidermis / metabolism Exosomes* / metabolism Fibroblasts / metabolism Humans Keratinocytes / metabolism Lentigo* / etiology Melanins / metabolism Photosensitivity Disorders* / metabolism Stem Cells / metabolism
IF 3.368
リソース情報
ヒト・動物細胞 SF8428(RCB0621)