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缺少中性粒细胞的FOXO3驱动结肠炎症和瘤发生

Jenisha Ghimire¹, Rida Iftikhar¹, Harrison M Penrose¹

¹Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.

International journal of molecular sciences

|June 10, 2023

概括

叉头盒O3 (FOXO3) 缺乏多态核中性粒细胞 (PMN) 通过增加脂质滴积和细胞迁移,促进炎症性肠病和结肠癌. 这种FOXO3介导的途径是结肠病理生物学中的关键因素.

科学领域:

胃肠病学胃肠病学
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

炎症性肠病 (IBD) 和结肠癌具有共同的病理途径,涉及多态核中性粒细胞 (PMN).
PMN激活与细胞内脂质滴滴 (LD) 积累有关,这是一个由转录因子叉头盒O3 (FOXO3) 负面调节的过程.

研究的目的:

研究FOXO3-LD调控网络在PMN介导的IBD和结肠癌中的作用.
确定FOXO3缺乏PMN在结肠病理生物学中的临床意义.

主要方法:

对LD和PLIN的患者组织和免疫细胞的分析2.
功能性评估小鼠腹PMNs与刺激的LDs和FOXO3缺乏.
对缺乏FOXO3的PMN进行转录基因分析,以识别差异表达基因 (DEG).
生物信息分析将DEG与IBD和结肠癌途径联系起来.

主要成果:

在PMN中缺乏FOXO3会增强它们的迁移活动,并改变与代谢,炎症和瘤发生相关的基因表达.
缺乏FOXO3的PMN (PMN-FOXO3₃₈₉) 的转录特征有效地将IBD和结肠癌组织与对照组织区分开来.
增加PMN-FOXO3₃₈₉的存在预测结肠癌的入侵和较差的患者存活率.
经过验证的DEGs,包括P2RX1,MGLL,MCAM,CDKN1A,RALBP1,CCPG1和PLA2G7,都与IBD和结肠癌的发病有关.

结论:

腹腔疾病和FOXO3介导的PMN功能是IBD和结肠癌中结肠病理生物学的关键贡献者.
该PMN-FOXO3₃₈₉签名作为IBD和结肠癌的潜在生物标志物.
针对PMN中的FOXO3-LD通路可能为IBD和结肠癌提供新的治疗策略.

关键词:

在FOXO3中使用FOXO3.IBD IBD IBD IBD IBD IBD IBD IBD IBD IBD IBD IBD IBD IBD IBD 在 LDs 中,使用 LDs.这是一个PMN,PMN是PMN.结肠癌是什么意思结肠癌是什么意思

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