lncRNA CRNDE通过ERK1/2通路影响溃疡性结肠炎小鼠体内巨噬细胞焦亡和M1型极化OA
Effect of lncRNA CRNDE on Macrophage Pyroptosis and M1-type Polarization in Ulcerative Colitis Mice via ERK1/2 Pathway
目的 探讨长链非编码RNA(lncRNA)CRNDE通过细胞外信号调节激酶 1/2(ERK1/2)通路对溃疡性结肠炎(ulcerative colitis,UC)小鼠巨噬细胞焦亡和M1 型极化的影响.方法 构建UC小鼠模型,检测结肠长度,进行疾病活动度指数评分以验证模型;另将RAW264.7 细胞分为Ctrl组、pcDNA-null组、pcDNA-CRNDE组、pcDNA-CRNDE+LY3214996 组.qRT-PCR、蛋白质印迹检测 lncRNA CRNDE 及cleaved-Caspase-1、cleaved-GSDMD、ERK1/2、磷酸化ERK1/2(p-ERK1/2)的表达水平,流式细胞术检测F4/80+CD86+巨噬细胞比例.结果 模型组疾病活动度指数评分升高、结肠缩短,lncRNA CRNDE 及cleaved-Caspase-1、cleaved-GSDMD、p-ERK1/2 表达上调,F4/80+CD86+巨噬细胞比例增加(P均<0.05);在RAW264.7 细胞中,pcDNA-CRNDE组的lncRNA CRNDE及cleaved-Caspase-1、cleaved-GSDMD、p-ERK1/2 表达较pcDNA-null组上调,加入LY3214996 后lncRNA CRNDE及cleaved-Caspase-1、cleaved-GSDMD、p-ERK1/2 表达下调(P均<0.05).结论 lncRNA CRNDE在UC小鼠中通过激活ERK1/2 途径,促进巨噬细胞焦亡和M1 型极化,是治疗UC的潜在靶点.
Objective To investigate the effect of long non-coding RNA(lncRNA)CRNDE on macrophage pyroptosis and M1 polarization in ulcerative colitis(UC)mice and the potential mechanism.Methods The UC mouse model was established,and colon length,disease activity index(DAI)were measured to validate the model.RAW264.7 cells were divided into 4 groups:Ctrl group,pcDNA-null group,pcDNA-CRNDE group,and pcDNA-CRNDE+LY3214996 group.The expression levels of lncRNA CRNDE,cleaved-Caspase-1,cleaved-GSDMD,ERK1/2,and phosphorylated ERK1/2(p-ERK1/2)were detected by qRT-PCR or Western blotting.The proportion of F4/80+CD86+macrophages was measured by flow cytometry.Results In the model group,the DAI score was increased,the colon length was shortened,and the expression levels of lncRNA CRNDE,cleaved-Caspase-1,cleaved-GSDMD,and p-ERK1/2 were upregulated,and the proportion of F4/80+CD86+macrophages was increased(all P<0.05).In RAW264.7 cells,lncRNA CRNDE and cleaved-Caspase-1、cleaved-GSDMD、p-ERK1/2 expression in the pcDNA-CRNDE group was upregulated when compared with that in the pcDNA-null group,and that was downregulated after LY3214996 treatment(all P<0.05).Conclusion lncRNA CRNDE promotes macrophage pyroptosis and M1 polarization in UC mice by activating the ERK1/2 pathway,sugges-ting it may be a potential therapeutic target for UC.
翡罗热·地里夏提;祖丽胡玛尔·阿力木江;杜进璇
新疆医科大学第六附属医院消化科,乌鲁木齐市,830000新疆医科大学第六附属医院全科医学科,乌鲁木齐市,830000新疆医科大学第六附属医院消化科,乌鲁木齐市,830000
医药卫生
溃疡性结肠炎lncRNA CRNDE巨噬细胞焦亡M1 型极化
ulcerative colitislncRNA CRNDEmacrophagepyroptosisM1 polarization
《医学分子生物学杂志》 2026 (1)
36-42,7
新疆维吾尔自治区自然科学基金(No.2023D01C423) This work was supported by a grant from the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2023D01C423)
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