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Title
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Involvement of eIF6 in external mechanical stretch-mediated murine dermal fibroblast function via TGF- pathway
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Author
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Abstract
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| External mechanical loading on a wound commonly increases fibrosis. Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in fibrosis in various models, including the mechanical force model. However, the underlying mechanism is unclear. Our previous experiments suggested that eukaryotic initiation factor 6 (eIF6) acted as a regulator of TGF-beta 1 expression, and negatively impact on collagen synthesis. Our current results showed that external mechanical stretching significantly increased COL1A1, TGF-beta 1 and eIF6 expression as well as dermal fibroblasts proliferation, both in vitro and in vivo. eIF6-deficient (eIF6(+/-)) cells exhibited significantly higher levels of COL1A1, and these levels increased further with external mechanical stretching, suggesting that mechanical stretching plays a synergistic role in promoting COL1A1 expression in eIF6(+/-) cells. Inhibition of TGF beta R I/II by LY2109761 decreased COL1A1 protein expression in eIF6(+/-) dermal fibroblasts in a cell stretching model, and attenuated granulation tissue formation in partial thickness wounds of eIF6(+/-) mice. These data suggest that mechanical stretching has a synergistic role in the expression of COL1A1 in eIF6(+/-) cells, and is mediated by activation of TGF beta RI/II. Taken together, our results indicate that eIF6 may be involved in external mechanical force-mediated murine dermal fibroblast function at least partly through the TGF-beta 1 pathway. |
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Language
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English
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Source (journal)
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Scientific reports. - London, 2011, currens
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Publication
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London
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Nature Publishing Group
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2016
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ISSN
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2045-2322
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DOI
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10.1038/SREP36075
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Volume/pages
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6
(2016)
, 12 p.
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Article Reference
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36075
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ISI
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000387309000001
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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