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IL-13 mediates collagen deposition via STAT6 and microRNA-135b : a role for epigenetics.

O’Reilly, S. and Ciechomska, M. and Fullard, N. and Przyborski, S. and van Laar, J.M. (2016) 'IL-13 mediates collagen deposition via STAT6 and microRNA-135b : a role for epigenetics.', Scientific reports., 6 . p. 25066.

Abstract

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-β1. 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-β1. 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.

Item Type:Article
Full text:(AM) Accepted Manuscript
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Full text:(VoR) Version of Record
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Status:Peer-reviewed
Publisher Web site:http://dx.doi.org/10.1038/srep25066
Publisher statement:This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Date accepted:04 April 2016
Date deposited:04 May 2016
Date of first online publication:26 April 2016
Date first made open access:No date available

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