临床口腔医学杂志2024，Vol.40Issue(4)：195-199,5.DOI:10.3969/j.issn.1003-1634.2024.04.002
小鼠舌白斑的转录组学特征和信号通路改变及白介素17A单抗治疗的实验研究
Experimental study on the transcriptomic characteristics and signaling pathway alteration in mouse tongue leu-koplakia and effect of anti-mouse IL-17A monoclonal antibody on leukoplakia
摘要
Abstract
Objective:To explore the transcriptomic characteristics and signal pathway changes of mouse tongue leu-koplakia formation and malignant progression,as well as the therapeutic effect of interleukin-17A(IL-17A)monoclonal anti-body on mouse tongue leukoplakia.Methods:RNA-sequence was performed on human normal tongue mucosa tissues(NM),tongue leukoplakia(OL)tissues with epithelial dysplasia from the same patient,normal mucosa tissues,and leukoplakia tis-sues(mOL)from the tongue of 4NQO-induced mice.After 12 weeks of 4NQO induction,the mice were divided into two groups:experimental group(intraperitoneal injection of anti-mouse IL-17A monoclonal antibody)and control group(intraper-itoneal injection of IgG1 isotype control antibody),the dosage of monoclonal antibody was 10 mg/kg/w.Tissue samples were collected after four weeks'injection.And the histopathology of the mouse tongues were performed by hematoxylin-eosin stai-ning(HE staining)and immunohistochemistry staining(IHC)of Ki67.In vitro,the leukoplakia cell lines(DOK,Leuk1)were stimulated with recombinant human IL-17A respectively and cell cycle was analyzed by flow cytometry.Results:Comprehen-sive analysis of the transcriptomic sequencing results of humans and mice showed that the IL-17 signaling pathway was signif-icantly upregulated during leukoplakia formation.The histopathological evaluation results after four weeks of Anti-mouse IL-17A monoclonal antibody treatment showed that 80％of the mouse tongues in the experimental group had mild to moderate epithelial dysplasia,while 20％had severe epithelial dysplasia.In the control group,40％had mild to moderate epithelial dys-plasia,40％had severe epithelial dysplasia,but 20％had infiltrating cancer.The results of Ki67 showed that the proportion of cells in the proliferation stage in the control group was significantly higher than that in the control group(P＜0.05).And flow cytometry showed that IL-17A stimulation led to more concentration of cells in the S-G2-M phase(P＜0.05).Conclusion:The IL-17 signaling pathway is significantly upregulated during the formation and malignant progression of leukoplakia in hu-man and mice tongues.Anti-mouse IL-17A monoclonal antibody has potential therapeutic effect on 4NQO-induced mouse tongue leukoplakia.IL-17A promotes the proliferation of leukoplakia cells.关键词
转录组测序/IL-17信号通路/4NQO小鼠口腔白斑模型/IL-17A单抗Key words
RNA-seq(RNA sequencing)/IL-17A signaling pathway/4-NQO mouse oral leukoplakia model/Anti-mouse IL-17A monoclonal antibody分类
口腔医学引用本文复制引用
韩馨怡,张倩倩,王子瑞,周曾同,唐国瑶,施琳俊,沈雪敏..小鼠舌白斑的转录组学特征和信号通路改变及白介素17A单抗治疗的实验研究[J].临床口腔医学杂志,2024,40(4):195-199,5.基金项目
国家自然科学基金项目(82370954,82170952) （82370954,82170952）
上海市卫生健康委员会2020年度综合医院中西医结合专项立项一般项目(ZHYY-ZXYJHZX-202016) （ZHYY-ZXYJHZX-202016）
上海交通大学医学院附属第九人民医院医学研究培育基金(JYZZ182) （JYZZ182）
上海交通大学医学院附属第九人民医院研究型学科(KQYJXK2021) （KQYJXK2021）
上海市教委口腔高峰学科——临床医学"研究型医师"(双百人)(2022sbr-slj) （双百人）
科技部国家重点研发计划(SQ2022YFC2400066) （SQ2022YFC2400066）
