P018 SOCS1 and 3 expression is determined by fibroblast phenotype in IPF

Prêle, C., Iosifidis, T., McAnulty, R., Pearce, D., Badrian, B., Jamieson, S., Ernst, M., Thompson, P., Laurent, G., Knight, D. and Mutsaers, S. (2016) P018 SOCS1 and 3 expression is determined by fibroblast phenotype in IPF. QJM: An International Journal of Medicine, 109 (Suppl. 1). S27-S28.

Abstract

STAT3 signaling is implicated in IPF pathogenesis but the mechanisms regulating STAT3 expression and function are unknown. SOCS1 and SOCS3 inhibit STAT3 signaling and reduced SOCS1 levels have been reported in IPF lung fibroblasts and is also associated with increased collagen production. Using IPF and control lung fibroblasts and tissue, the mechanisms underlying SOCS1 downregulation in IPF were investigated. A significant reduction in basal SOCS1 mRNA in IPF fibroblasts was confirmed and a trend towards reduced SOCS3 demonstrated. However there was no difference in their ability to phosphorylate STAT1 or STAT3 or increase SOCS3 expression following IL-6 stimulation or to phosphorylate STAT1 and increase SOCS1 mRNA after IFNγ treatment. Methylation of SOCS1 in control and IPF fibroblasts was low and unaffected by 5’-aza-2’-deoxycytidine’ treatment. SOCS1 is a target of microRNA (miR)-155 and although the miR155 level was increased in IPF tissue, expression was reduced in IPF fibroblasts. Therefore, SOCS1 is not regulated by mRNA stability, SOCS1 gene methylation or miR155 in these cells. Interestingly, reanalysis of cells based on collagen (COLIA1) and alpha smooth muscle actin (ACTA2) mRNA levels showed that cells classified as fibrotic (high COLIA1 and ACTA2), actually had increased SOCS1 and SOCS3 mRNA levels, opposite to the original findings when grouped based on clinical diagnosis. In conclusion, these findings question the role of SOCS1 in driving lung fibrosis in IPF, and demonstrate that phenotypic characterization, in addition to clinical diagnosis will provide a more complete picture of the differential behaviour between IPF and normal lung fibroblasts.

Item Type:	Journal Article
Publisher:	Oxford University Press on behalf of the Association of Physicians
Copyright:	© 2016 The Authors.
URI:	http://researchrepository.murdoch.edu.au/id/eprint/64332

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