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Reduced socs1 expression in lung fibroblasts from patients with ipf is not mediated by promoter methylation or mir155

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journal contribution
posted on 21.06.2021, 01:45 by CM Prêle, T Iosifidis, RJ McAnulty, DR Pearce, B Badrian, T Miles, SE Jamieson, Matthias ErnstMatthias Ernst, PJ Thompson, GJ Laurent, DA Knight, SE Mutsaers
The interleukin (IL)-6 family of cytokines and exaggerated signal transducer and activator of transcription (STAT)3 signaling is implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis, but the mechanisms regulating STAT3 expression and function are unknown. Suppressor of cytokine signaling (SOCS)1 and SOCS3 block STAT3, and low SOCS1 levels have been reported in IPF fibroblasts and shown to facilitate collagen production. Fibroblasts and lung tissue from IPF patients and controls were used to examine the mechanisms underlying SOCS1 down-regulation in IPF. A significant reduction in basal SOCS1 mRNA in IPF fibroblasts was confirmed. However, there was no difference in the kinetics of activation, and methylation of SOCS1 in control and IPF lung fibroblasts was low and unaffected by 5′-aza-2′-deoxycytidine’ treatment. SOCS1 is a target of microRNA-155 and although microRNA-155 levels were increased in IPF tissue, they were reduced in IPF fibroblasts. Therefore, SOCS1 is not regulated by SOCS1 gene methylation or microRNA155 in these cells. In conclusion, we confirmed that IPF fibroblasts had lower levels of SOCS1 mRNA compared with control fibroblasts, but we were unable to determine the mechanism. Furthermore, although SOCS1 may be important in the fibrotic process, we were unable to find a significant role for SOCS1 in regulating fibroblast function.

Funding

This project was initiated and supported in part by NHMRC project grants 458703, 458543 (S.E.M., D.A.K., M.E.), UWA Faculty of Medicine and Dentistry Seeding Grant (C.M.P.) and Sir Charles Gairdner Hospital Research Advisory Committee Grant (P.J.T.). C.M.P. was a recipient of a Raine Medical Research Foundation Grant-in-aid.

History

Publication Date

30/04/2021

Journal

Biomedicines

Volume

9

Issue

5

Article Number

498

Pagination

13p.

Publisher

MDPI

ISSN

2227-9059

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