Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts

    Naomi A. Carne, Steven Bell, Adrian P. Brown, Arto Määttå, Michael J. Flagler, Adam M. Benham
    TLDR Reductive stress messes up collagen balance and alters cell signaling in human skin cells, which could help treat certain skin diseases.
    In the 2019 study, researchers found that reductive stress, induced by dithiothreitol (DTT), selectively disrupted collagen homeostasis and modified signaling through the MAPK/Akt pathway in human dermal fibroblasts. Proteomic analysis revealed that out of 4487 proteins, only 42 showed significant changes, with a notable reduction in specific collagens and extracellular matrix components. The study demonstrated that reductive stress caused chronic dephosphorylation of ERK1/2 and increased phosphorylation of Akt, independent of growth factors. These findings suggest that collagens are key molecules affected by redox stress, which could be targeted to treat skin diseases related to improper matrix deposition.
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