4.6 Article

UVB-Induced ciRS-7 Activates Melanogenesis by Paracrine Effects

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DNA AND CELL BIOLOGY
卷 40, 期 3, 页码 523-531

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MARY ANN LIEBERT, INC
DOI: 10.1089/dna.2020.5489

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CiRS-7; melanogenesis; Ultraviolet B; paracrine effects; FGF2

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The study reveals that ciRS-7 triggers melanogenesis in melanocytes through regulation of the miR-7/STAT3 and AKT/FGF2 paracrine axis in keratinocytes and fibroblasts. This mechanism may play a critical role in the development of pigmented skin diseases.
Antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as or ciRS-7) is an important member of the circular RNA family and is involved in the regulation of numerous biological functions. Keratinocytes and fibroblasts (FBs) affect melanogenesis through paracrine effects. However, whether ciRS-7 is involved in melanogenesis by regulating paracrine effects remains unclear. This study demonstrates for the first time that ciRS-7 is highly expressed in keratinocytes, FBs, and melanocytes (MCs). Ultraviolet B (UVB) irradiation promotes ciRS-7 expression in keratinocytes and FBs. Following inhibition of ciRS-7 expression in keratinocytes and FBs, the culture supernatant from these cells inhibited melanogenesis of MCs. Further analyses revealed that the expression and secretion of fibroblast growth factor 2 (FGF2) and phosphorylation of STAT3 and AKT in keratinocytes and FBs were significantly downregulated following inhibition of ciRS-7 expression, whereas the level of miR-7 was increased. Overexpression of miR-7 in keratinocytes and FBs significantly inhibited the expression of FGF2. In conclusion, our findings demonstrate that UVB-induced ciRS-7 triggers melanogenesis in MCs through regulation of the miR-7/STAT3 and AKT/FGF2 paracrine axis in both keratinocytes and FBs. ciRS-7 may serve as a regulator in the development of pigmented skin diseases.

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