lnc-MRGPRF-6:1 Promotes M1 Polarization of Macrophage and Inflammatory Response through the TLR4-MyD88-MAPK Pathway.

ABSTRACT

BACKGROUND: Macrophage-mediated inflammation plays an essential role in the development of atherosclerosis (AS). Long noncoding RNAs (lncRNAs), as crucial regulators, participate in this process. We identified that lnc-MRGPRF-61 was significantly upregulated in the plasma exosomes of coronary atherosclerotic disease (CAD) patients in a preliminary work. In the present study, we aim to assess the role of lnc-MRGPRF-61 in macrophage-mediated inflammatory process of AS. METHODS: The correlation between lnc-MRGPRF-61 and inflammatory factors was estimated firstly in plasma exosomes of CAD patients. Subsequently, we established lnc-MRGPRF-61 knockout macrophage model via the CRISPR/Cas9 system. We then investigated the regulatory effects of lnc-MRGPRF-61 on macrophage polarization and foam cell formation. Eventually, transcriptome analysis by RNA sequencing was carried out to explore the contribution of differential genes and signaling pathways in this process. RESULTS: lnc-MRGPRF-61 was highly expressed in the plasma exosomes of CAD patients and was positively correlated with the expression of inflammatory cytokines in plasma. lnc-MRGPRF-61 inhibition significantly reduced the formation of foam cells. The expression of lnc-MRGPRF-61 was upregulated in M1 macrophage, and lnc-MRGPRF-61 knockout decreased the polarization of M1 macrophage. lnc-MRGPRF-61 regulates macrophage polarization via the TLR4-MyD88-MAPK signaling pathway. CONCLUSIONS: lnc-MRGPRF-61 knockdown can inhibit M1 polarization of macrophage and inflammatory response through the TLR4-MyD88-MAPK signaling pathway. lnc-MRGPRF-61 is a vital regulator in macrophage-mediated inflammatory process of AS.