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LSC Abstract – Investigating SOCS-mediated regulation of STAT signalling in idiopathic pulmonary fibrosis (IPF)

Prêle, C., Iosifidis, T., McAnulty, R., Badrian, B., Jamieson, S., Pearce, D., Ernst, M., Thompson, P., Laurent, G., Knight, D. and Mutsaers, S. (2016) LSC Abstract – Investigating SOCS-mediated regulation of STAT signalling in idiopathic pulmonary fibrosis (IPF). European Respiratory Journal, 48 . PP202.

Link to Published Version: https://doi.org/10.1183/13993003.congress-2016.PP2...
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Abstract

The STAT inhibitor, SOCS1 is reduced in IPF lung fibroblasts, and has been linked to higher levels of type I collagen. Using IPF (n=6) and control (n=9) lung fibroblast cultures and control (n=4) and IPF (n=8) lung tissue, we investigated the mechanisms underlying SOCS1 down-regulation in IPF. We have demonstrated a significant reduction in basal SOCS1 mRNA in IPF fibroblasts and have observed a trend towards reduced SOCS3. Immunohistochemical analysis of lung tissue revealed an abundance of activated-STAT1 and -STAT3, target molecules of SOCS1 and SOCS3. There was no difference in collagen mRNA between IPF and control fibroblasts but high basal levels of collagen protein were detected in IPF cells. There was no difference in the ability of IPF fibroblasts to express pSTAT1, pSTAT3 or SOCS3 following IL-6 stimulation, although the magnitude of the response varied. Similarly, the kinetics of IFNγ-induced SOCS1 mRNA and pSTAT1 levels were not altered in IPF fibroblasts. SOCS1 has been identified as a target of miR155, so we investigated the capacity of miR155 to regulate SOCS1 in IPF. miR155 levels were significantly increased in IPF lung tissue, providing a possible explanation for reduced SOCS1. However, miR155 was reduced in IPF fibroblasts. Analysis of the methylation pattern at putative STAT1/3 binding sites within the SOCS1 promoter has revealed that these sites are unmethylated. In conclusion SOCS1 expression in human lung fibroblasts is not regulated by methylation at STAT1/3 transcription factor binding sites in the SOCS1 promoter or by miR155.

Item Type: Journal Article
Publisher: European Respiratory Society
Copyright: © 2016 The Authors.
Other Information: 14th Lung Science Conference. Estoril, Portugal 10-13 March, 2016
URI: http://researchrepository.murdoch.edu.au/id/eprint/64330
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