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Lookup NU author(s): Dr Steven O'Reilly, Dr Marzena Ciechomska, Dr Nicola Fullard, Professor Jaap van Laar
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Systemic sclerosis is an autoimmune connective tissue disease in which T cells play a prominent role. We and others have previously demonstrated a role for T cell-derived IL-13 in mediating the induction of collagen in dermal fibroblasts and that blockade with IL-13 antibodies attenuates this increase. In this study we want to probe the signalling that underpins IL-13 mediated matrix deposition. Isolated dermal fibroblasts were incubated with recombinant IL-13 and gene expression by qRT-PCR was performed for collagen1A1 and TGF-beta 1. Small interfering RNA (siRNA) was used to knock down STAT6 and a small molecule inhibitor was also used to block this pathway. MiR-135b was transfected into fibroblasts plus and minus IL-13 to see if this miR plays a role. miR-135b was measured in systemic sclerosis fibroblasts isolated from patients and also in serum. Results showed that IL-13 increased collagen expression and that this is independent from TGF-beta 1. This is dependent on STAT6 as targeting this blocked induction. MiR-135b reduces collagen induction in fibroblasts and scleroderma fibroblasts have lower constitutive levels of the miR. We further demonstrate that miR135b is repressed by methylation and may include MeCP2. In conclusion we show that STAT6 and miR-135b regulate IL-13-mediated collagen production by fibroblasts.
Author(s): O'Reilly S, Ciechomska M, Fullard N, Przyborski S, van Laar JM
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2016
Volume: 6
Online publication date: 26/04/2016
Acceptance date: 04/04/2016
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/srep25066
DOI: 10.1038/srep25066
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