Suppression of mir-150-5p attenuates the anti-inflammatory effect of glucocorticoids in mice with ulcerative colitis
Suppression of mir-150-5p attenuates the anti-inflammatory effect of glucocorticoids in mice with ulcerative colitis
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DOI：
10.1016/j.molimm.2023.09.002
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发表时间：
2023-11-01
影响因子：
3.6
通讯作者：
Yang，Jilin
中科院分区：
文献类型：
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作者：
Wang，Yijie;Qin，Jiahong;Yang，Jilin
糖皮质激素已被广泛用于治疗溃疡性结肠炎，但由于激素抵抗，并非所有患者都能从这种治疗中获益。据报道，Mir-150- 5 p可增强糖皮质激素的疗效，低血清mir-150- 5 p表达与溃疡性结肠炎患者的糖皮质激素抵抗有关。本研究的目的是阐明mir-150- 5 p调控糖皮质激素抵抗的机制。采用溃疡性结肠炎小鼠模型评价溃疡性结肠炎症状、炎症因子和糖皮质激素耐药相关基因表达的变化。结果显示，用替吉奥抑制mir-150- 5 p并不显著干扰或增强葡聚糖硫酸钠诱导的溃疡性结肠炎症状，但它确实通过异常调节IL-17 a、IL-10、IL-2和IL-6水平的表达和髓过氧化物酶活性来减弱地塞米松的炎症抑制作用。Mir-150- 5 p抑制还诱导溃疡性结肠炎小鼠结肠组织中糖皮质激素抗性基因表达谱，上调p-ERK、p-JNK和HSP 90，下调p-GRa、FKBP 4和HDAC 2表达。我们的研究结果表明，miR-150- 5 p抑制减弱糖皮质激素的抗炎作用，并可能作为一个驱动因素在溃疡性结肠炎糖皮质激素resistance.Availability的数据和materialsAll数据和数字分析在这项研究中可从相应的作者的要求。
Glucocorticoids have been widely used in the treatment of ulcerative colitis, but not all patients benefit from this therapy due to hormone resistance. Mir-150–5p has been reported to enhance the efficacy of glucocorticoids, and low serum mir-150–5p expression has been linked to glucocorticoid resistance in ulcerative colitis patients. The aim of this study was to elucidate the mechanisms of mir-150–5p regulation on glucocorticoid resistance. An ulcerative colitis mouse model was used to evaluate changes in ulcerative colitis symptoms, inflammatory factors, and glucocorticoid resistance-related gene expression. The results showed that mir-150–5p suppression with antagomirs did not significantly interfere with or enhance the induction of ulcerative colitis symptoms by dextran sulfate sodium, but it did attenuate the inflammation inhibitory effect of dexamethasone by abnormally regulating the expression of IL-17a, IL-10, IL-2 and IL-6 levels and myeloperoxidase activity. Mir-150–5p inhibition also induced a glucocorticoid-resistant gene expression profile in colon tissues of ulcerative colitis mice, with upregulation of p-ERK, p-JNK, and HSP90 and downregulation of p-GRa, FKBP4, and HDAC2 expression. Our results indicate that mir-150–5p suppression attenuates the anti-inflammatory effect of glucocorticoids and may function as a driver element in ulcerative colitis glucocorticoid resistance.Availability of data and materialsAll data and figures analyzed in this study are available from the corresponding author by request.