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

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.

NLRP3 inflammasome mediates chronic intermittent hypoxia‐induced renal injury implication of the microRNA‐155/FOXO3a signaling pathway

“…In addition, miR-155 control NLRP3 inflammasome and IL-1β cytokine signaling cascade through a positive feedback loop, thus enhancing inflammatory cytokines production. Consistent with our results, another recent study has demonstrated that miR-155 is dependent on the NLRP3 inflammasome activation, for miR-155 expression could be blocked when inflammasome was inhibited (Artlett, Sassi-Gaha, Hope, Feghali-Bostwick, & Katsikis, 2017). H. reported that overexpression of miR-155 resulted in increased levels of caspase-1, IL-1β, and IL-18, whereas knockdown of miR-155 attenuated the inflammatory cell death of HK-2 cells, indicating that anti-miR-155 could be a strategy for the prevention of renal pyroptosis.…”

SHIP‐1, a target of miR‐155, regulates endothelial cell responses in lung fibrosis

“…MicroRNAs (miRNAs) play important roles in regulating gene expression and specific miRNAs participate in the fibrotic process in different tissues and organs . MiRNA‐155 (miR‐155), a pro‐inflammatory factor via SHIP‐1 downregulation, has been identified as having immune regulatory functions and plays a critical role in tissue fibrosis in liver and lung . However, contradictory effects of miR‐155, pro‐fibrotic and anti‐fibrotic, in experimental and idiopathic pulmonary fibrosis, have been reported …”

“…[7][8][9] MiRNA-155 (miR-155), a pro-inflammatory factor via SHIP-1 downregulation, has been identified as having immune regulatory functions and plays a critical role in tissue fibrosis in liver and lung. [10][11][12][13] However, contradictory effects of miR-155, pro-fibrotic and anti-fibrotic, in experimental and idiopathic pulmonary fibrosis, have been reported. 11,14 Several studies proposed the concept that lung endothelial cells and endothelial-mesenchymal transition (EndoMT) play important roles in the pathogenesis of pulmonary fibrosis.…”

Silencing of miR‑155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation

“…In the present study, addition of an NLRP3 inhibitor reversed the miR-155 mediated increased inflammation in keratinocyte-induced HaCaT cells. Artlett et al (23) reported that miR-155 required NLRP3 inflammasome-mediated collagen synthesis during fibrosis.…”