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

O’Reilly, S.; Ciechomska, M.; Fullard, N.; Przyborski, S.; van Laar, J.M.

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


Authors

S. O’Reilly

M. Ciechomska

J.M. van Laar



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.

Citation

O’Reilly, S., Ciechomska, M., Fullard, N., Przyborski, S., & van Laar, J. (2016). IL-13 mediates collagen deposition via STAT6 and microRNA-135b: a role for epigenetics. Scientific Reports, 6, Article 25066. https://doi.org/10.1038/srep25066

Journal Article Type Article
Acceptance Date Apr 4, 2016
Online Publication Date Apr 26, 2016
Publication Date Apr 26, 2016
Deposit Date Apr 29, 2016
Publicly Available Date May 4, 2016
Journal Scientific Reports
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 6
Article Number 25066
DOI https://doi.org/10.1038/srep25066

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http://creativecommons.org/licenses/by/4.0/

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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/






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