Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis
| Autor: | Sihem Sassi-Gaha, Carol Feghali-Bostwick, Jennifer L. Hope, Peter D. Katsikis, Carol M. Artlett |
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| Přispěvatelé: | Immunology |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Diseases of the musculoskeletal system Inflammasomes miR-155 03 medical and health sciences 0302 clinical medicine Fibrosis Pulmonary fibrosis microRNA NLR Family Pyrin Domain-Containing 3 Protein medicine Humans Scleroderma Systemic integumentary system business.industry IL-1 Interleukin Inflammasome Fibroblasts medicine.disease NLRP3 inflammasome 3. Good health MicroRNAs 030104 developmental biology Real-time polymerase chain reaction 030220 oncology & carcinogenesis Immunology Cancer research Systemic sclerosis Collagen lcsh:RC925-935 business Myofibroblast medicine.drug Research Article |
| Zdroj: | Arthritis Research & Therapy, Vol 19, Iss 1, Pp 1-8 (2017) Arthritis Research & Therapy Arthritis Research & Therapy, 19:144. BioMed Central Ltd. |
| ISSN: | 1478-6362 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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