Abstract
To explore the effect and potential mechanism of LncRNA MIR4435-2HG on macrophage polarization and intestinal inflammation in ulcerative colitis (UC). Methods RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS) were co-cultured with Caco-2 cells to establish an inflammatory model of UC in vitro. Balb/c mice were orally administered dextran sulfate sodium (DSS) to establish an in vivo UC model. Flow cytometry and immunohistochemical (IHC) analyses were performed to assess the levels of surface phenotype markers. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were performed to measure the levels of inflammatory cytokines. Western blotting was used to analyze expression of the tight junction protein zona occludens 1 (ZO-1) and the key proteins of the JAK1/STAT1 signaling pathway (Janus kinase-1(JAK1), p-JAK1, signal transducer and activator of transcription 1 (STAT1), p-STAT1. Results In in vitro experiments, we found that inhibition of MIR4435-2HG was able to decrease the levels of CD68, iNOS, IL-6, and TEER, and increase the levels of CD206, Arg-1, IGF-1, and ZO-1. Meanwhile, inhibition of MIR4435-2HG significantly suppressed the levels of p- JAK1 and p- STAT1. In addition, we further demonstrated by in vivo experiments that inhibition of MIR4435-2HG significantly attenuated intestinal inflammation in mice, as evidenced by increased body weight, increased colon length and weight, decreased fecal scores, hemorrhagic scores, and DAI scores, and amelioration of colonic injury, and decreased inflammatory factors. Conclusions MIR4435-2HG suppression inhibits macrophage M1 polarization while promoting M2 polarization, thereby alleviating intestinal inflammation in mice with ulcerative colitis through JAK1/STAT1 signaling.