Liposomal nanoparticle-based miR-155 antagonist regulates Th17/Treg signaling pathway and its inhibitory effect against myocarditis

Abstract

Abnormal expression of miR-155 is related to degree of myocardial fibrosis in myocarditis. This study mainly explored the role of miR-155 in myocardial fibrosis and possible mechanisms. Forty Balb/c mice were randomly separated into blank group, model group, miR-155 group, and DMSO group (n = 10). Fibrosis area and expression of TGF-β and α-SMA in each group were observed. Fibroblasts were then isolated and miR-155mRNA expression, expression of Collagen I, α-SMA, Th17 cell number, Treg cell number, and expressions of IL-6, IL-10, IL-17, STAT3, RORγt, and Foxp3 were also investigated. The model group and DMSO group had the highest fibrosis area, while the blank group and miR-155 group had the lowest fibrosis area. However, the fibrosis area for miR-155 group was higher than the blank group (P >0.05). No significant difference was found between model group and DMSO group (P >0.05). Compared to blank and miR-155 groups, expressions of TGF-β and α-SMA in the model and DMSO group were significantly up-regulated (P <0.05). No significant difference was found between the model and DMSO groups, or between blank and miR-155 groups P < 0.05). Compared to blank and miR-155 groups, the levels of Collagen I, α-SMA, IL-6, IL-10, IL-17, STAT3, RORγt, and Foxp3 in the model and DMSO groups were significantly up-regulated (P > 0.05). No significant difference was found between model and DMSO groups, or between blank and miR-155 groups (P < 0.05). The number of Th17 cells was significantly increased, while Treg cells were significantly decreased in the model and DMSO groups (P < 0.05). In contrast, Th17 cells were significantly decreased, while Treg cells were significantly increased in the blank and miR-155 groups (P < 0.05). No significant difference was found between the model and DMSO groups, or between blank and miR-155 groups (P < 0.05). Moreover, miR-155 inhibited myocarditis and myocardial fibrosis. The mechanism is mainly related to Th17/Treg signaling pathway, where miR-155 decreased Th17 cells, increased Treg cells, inhibited the secretion of Collagen I and α-SMA, and reduced the levels of fibroblast molecules. The miR-155 also interacted with STAT3 pathway to stimulate the activity of inflammatory cells, inhibit the secretion of inflammatory factors, further improving the inflammatory response of myocarditis, and ultimately improving the degree of myocarditis myocardial fibrosis.