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- W2800576711 abstract "Normal human dermal fibroblasts (NHDF) are responsible for the production of extracellular matrix (ECM) proteins. Transforming growth factor (TGF)-ß1 causes the differentiation of NHDF into myofibroblasts and an increase in ECM protein production. Insulin-like growth factor (IGF)-1 is associated with fibroblast proliferation and tissue fibrosis. We postulate that there is a link between IGF and TGF-ß signalling in NHDF, and by modifying downstream signalling it is possible to rejuvenate dermal reticular fibroblasts. Using an immunostaining assay and the Operetta high-content imaging system NHDF phenotype was assessed. Treated with agonists and inhibitors of the TGF-ß signalling pathway, NHDF were assayed for differentiation, proliferation and shape. Using the Agilent one-colour microarray system NHDF genotype was determined. The Fluidigm high-throughput qPCR system was used to validate the microarray gene expression profiles. TGF-ß1 caused a significant increase in NHDF proliferation and a significant decrease in the proportion of ‘spindle-shaped’ cells. One of four donor NHDF expressed significantly lower α-(SMA) smooth muscle actin in response to TGF-ß1 treatment. A gene expression profile for this low α-SMA NHDF was gained (IGF-1: increased expression, p-value=1.08E-02) and validated (IGF-1: increased expression, p-value=4.69E-06). Ongoing work involving stable lentiviral treatment will help to determine the extent to which the target genes are involved in NHDF fibrosis; identifying possible crosstalk between signalling pathways which effect NHDF phenotype." @default.
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- W2800576711 date "2018-05-01" @default.
- W2800576711 modified "2023-09-28" @default.
- W2800576711 title "857 Fibroblast heterogeneity in human adult dermis: IGF-1/TGF-β1 signal modification to rejuvenate reticular fibroblasts" @default.
- W2800576711 doi "https://doi.org/10.1016/j.jid.2018.03.868" @default.
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