Affordable Access

Access to the full text

Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis

Authors
  • Artlett, Carol M.1
  • Sassi-Gaha, Sihem1
  • Hope, Jennifer L.1, 2
  • Feghali-Bostwick, Carol A.3
  • Katsikis, Peter D.1, 2
  • 1 Drexel University College of Medicine, Department of Microbiology and Immunology, 2900 Queen Lane, Philadelphia, PA, 19129, USA , Philadelphia (United States)
  • 2 Erasmus University Medical Center, Department of Immunology, Rotterdam, The Netherlands , Rotterdam (Netherlands)
  • 3 Medical University of South Carolina, Division of Rheumatology & Immunology, Charleston, SC, USA , Charleston (United States)
Type
Published Article
Journal
Arthritis Research & Therapy
Publisher
Springer Science and Business Media LLC
Publication Date
Jun 17, 2017
Volume
19
Issue
1
Identifiers
DOI: 10.1186/s13075-017-1331-z
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundDespite the important role that microRNAs (miRNAs) play in immunity and inflammation, their involvement in systemic sclerosis (SSc) remains poorly characterized. miRNA-155 (miR-155) plays a role in pulmonary fibrosis and its expression can be induced with interleukin (IL)-1β. SSc fibroblasts have activated inflammasomes that are integrally involved in mediating the myofibroblast phenotype. In light of this, we investigated whether miR-155 played a role in SSc and if its expression was dependent on inflammasome activation.MethodsmiR-155 expression was confirmed in SSc dermal and lung fibroblasts by quantitative polymerase chain reaction (PCR). Wild-type and NLRP3-deficient murine fibroblasts were utilized to explore the regulation of miR-155 during inflammasome activation. miR-155-deficient fibroblasts and retroviral transductions with a miR-155 expression or control vectors were used to understand the contribution of miR-155 in fibrosis.ResultsmiR-155 was significantly increased and the highest expressing miRNA in SSc lung fibroblasts. Its expression was dependent on inflammasome activation as miR-155 expression could be blocked when inflammasome signaling was inhibited. In the absence of miR-155, inflammasome-mediated collagen synthesis could not be induced but was restored when miR-155 was expressed in miR-155-deficient fibroblasts.ConclusionsmiR-155 is upregulated in SSc. These results suggest that the inflammasome promotes the expression of miR-155 and that miR-155 is a critical miRNA that drives fibrosis.

Report this publication

Statistics

Seen <100 times