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- W4366184460 abstract "Neprilysin (NPL) is a wrinkle-inducing membrane bound elastase that is expressed abundantly in UV-exposed and in aged dermal fibroblasts (JBC2010). The overexpression of NPL is essentially associated with enhanced epithelial-mesenchymal cytokine interactions (EMCI) mainly via IL-1α which has a distinct potential to stimulate the expression of NPL by human dermal fibroblasts (HDFs)(BJ2012). The over-expression of NPL also accelerates wrinkle formation, accompanied by disruptions of the three-dimensional architecture of dermal elastic fibers responsible for the loss of skin elasticity (JID 2001). Because signaling pathways leading to the IL-1a-stimulated expression of NPL in HDFs remain unclear, we characterized the signaling pathway involved, including its transcription factor, in IL-1a-treated HDFs. Since qRT-PCR analysis revealed that the mRNA expression level of NPL is stimulated to a stronger extent in adult HDFs (HDFa) by IL-1a than in neonatal HDFs, we used HDFa in the signaling analysis. Western blotting analysis of the phosphorylation of signaling factors revealed that IL-1α significantly stimulated the phosphorylation of ERK1/2, JNK, p38, MSK1, NFkB, c-Jun, ATF2 and STAT3. Analysis using signaling inhibitors demonstrated that inhibitors of ERK and JNK but not p38, MSK1, NFkB or STAT3 significantly abrogated the IL-1α stimulated expression of NPL at the mRNA, protein and activity levels. Furthermore, c-Fos silencing significantly downregulated the IL-1α-increased expression of NPL at the protein and activity levels. These findings strongly suggest that the IL-1α-stimulated expression of NPL in HDFa is mediated via an intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1." @default.
- W4366184460 created "2023-04-19" @default.
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- W4366184460 date "2023-05-01" @default.
- W4366184460 modified "2023-09-28" @default.
- W4366184460 title "1142 The IL-1α stimulated expression of the wrinkle-inducing elastase neprilysin in adult human dermal fibroblasts is mediated via an intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1" @default.
- W4366184460 doi "https://doi.org/10.1016/j.jid.2023.03.1155" @default.
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