Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis
Abstract Background Despite 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...
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doaj-a8c9561d26774d778d9b845e5945974b2020-11-25T00:49:51ZengBMCArthritis Research & Therapy1478-63622017-06-011911810.1186/s13075-017-1331-zMir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosisCarol M. Artlett0Sihem Sassi-Gaha1Jennifer L. Hope2Carol A. Feghali-Bostwick3Peter D. Katsikis4Department of Microbiology and Immunology, Drexel University College of MedicineDepartment of Microbiology and Immunology, Drexel University College of MedicineDepartment of Microbiology and Immunology, Drexel University College of MedicineDivision of Rheumatology & Immunology, Medical University of South CarolinaDepartment of Microbiology and Immunology, Drexel University College of MedicineAbstract Background Despite 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. Methods miR-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. Results miR-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. Conclusions miR-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.http://link.springer.com/article/10.1186/s13075-017-1331-zFibrosisNLRP3 inflammasomemiR-155Systemic sclerosisIL-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carol M. Artlett Sihem Sassi-Gaha Jennifer L. Hope Carol A. Feghali-Bostwick Peter D. Katsikis |
spellingShingle |
Carol M. Artlett Sihem Sassi-Gaha Jennifer L. Hope Carol A. Feghali-Bostwick Peter D. Katsikis Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis Arthritis Research & Therapy Fibrosis NLRP3 inflammasome miR-155 Systemic sclerosis IL-1 |
author_facet |
Carol M. Artlett Sihem Sassi-Gaha Jennifer L. Hope Carol A. Feghali-Bostwick Peter D. Katsikis |
author_sort |
Carol M. Artlett |
title |
Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis |
title_short |
Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis |
title_full |
Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis |
title_fullStr |
Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis |
title_full_unstemmed |
Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis |
title_sort |
mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for nlrp3 inflammasome-mediated collagen synthesis during fibrosis |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2017-06-01 |
description |
Abstract Background Despite 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. Methods miR-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. Results miR-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. Conclusions miR-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. |
topic |
Fibrosis NLRP3 inflammasome miR-155 Systemic sclerosis IL-1 |
url |
http://link.springer.com/article/10.1186/s13075-017-1331-z |
work_keys_str_mv |
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