MiR-155-5p-SOCS1/JAK1/STAT1 participates in hepatic lymphangiogenesis in liver fibrosis and cirrhosis by regulating M1 macrophage polarization

Abstract

Background The role and underlying mechanism of liver macrophages and their derived miR-155-5p in hepatic lymphangiogenesis in liver fibrosis remain unclear. Here, we investigated the mechanism by which macrophages and miR-155-5p were involved in lymphangiogenesis during liver fibrosis and cirrhosis. Methods In vivo, hepatic lymphatic vessel expansion was evaluated; the liver macrophage subsets, proportion of peripherally-derived macrophages and expressions of CCL25, MCP-1, VAP-1 and MAdCAM-1 were documented; and miR-155-5p in the peripheral blood and liver was detected. In vitro, macrophages with miR-155-5p overexpression and inhibition were used to clarify the effect of miR-155-5p on regulation of macrophage polarization and the possible signalling pathway. Results Hepatic lymphangiogenesis was observed in mice with liver fibrosis and cirrhosis challenged with carbon tetrachloride (CCl4). In the liver, the number of M1 macrophages was associated with lymphangiogenesis and the degree of fibrosis. The liver recruitment of peripherally-derived macrophages occurred during liver fibrosis. The levels of miR-155-5p in the liver and peripheral blood gradually increased with aggravation of liver fibrosis. In vitro, SOCS1, a target of miR-155-5p, regulated macrophage polarization into the M1 phenotype through the JAK1/STAT1 pathway. Conclusion MiR-155-5p-SOCS1/JAK1/STAT1 pathway participates in hepatic lymphangiogenesis in mice with liver fibrosis and cirrhosis induced by CCl4 by regulating the polarization of macrophages into the M1 phenotype.

Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors

“…STAT1 and STAT6 are also involved in regulating macrophage polarization. Specifically, the STAT1 pathway facilitates macrophage polarization to the M1 phenotype [ [229] , [230] , [231] , [232] , [233] ], whereas the STAT6 pathway promotes macrophage polarization to the M2 phenotype [ [234] , [235] , [236] ]. Upregulation of STAT6 expression in TAMs leads to their polarization to the M2 phenotype and plays a role in regulating tumor angiogenesis [ 237 ].…”

The macrophage polarization by miRNAs and its potential role in the treatment of tumor and inflammation (Review)

“…This finding provides new insights into the development of novel therapeutic strategies for combatting HBV + HCC and a new reference for exploring antitumor immunotherapy ( 61 ). Recently, it has been reported that miR-155-5p can regulate M1-type macrophage polarization by targeting downstream SOCS1/JAK1/STAT1 axis and participate in liver fibrosis and hepatic lymphangiogenesis in cirrhosis ( 62 ). Besides, miR-155-5p can regulate M1 polarization by other pathways, such as SOCS1/NF-κB pathway ( 63 ), and let-7a-5p can also target suppressor of cytokine signaling 1 (SOCS1) to modulate NF-κB, and activate M1 macrophages ( 64 ).…”