CAJ | 학술논문

目的：探索信号转导与转录因子4(STAT4)对髓系抑制性细胞(MDSCs)动员和分化的调控及其在结肠癌发生发展中的作用。方法应用信号转导与转录激活因子4基因敲除( STAT4-/-)小鼠建立炎症相关肠癌模型,STAT4-/-小鼠通过腹腔注射氧化偶氮甲烷( AOM)和饮用含DSS水诱发急性肠炎,建立炎症相关结肠肿瘤模型并鉴定；应用流式细胞技术分析STAT4基因缺失对免疫细胞亚群分化和动员的影响。结果 STAT4-/-小鼠表现为明显的结肠肿瘤病变,而野生型( WT )对照组在结肠的中下段和肛门处只有炎性病变和上皮组织增生；CD11b﹢Gr-1﹢MDSCs在 STAT4-/-小鼠的外周血、脾脏和骨髓内的百分率较 WT 对照组小鼠显著增加( P ＜0.05)。结论 STAT4缺失能促进小鼠结肠肿瘤的发生,其机制可能与STAT4信号通路抑制导致CD11b﹢Gr-1﹢MDSCs的异常分化和动员有关。
목적：탐색신호전도여전록인자4(STAT4)대수계억제성세포(MDSCs)동원화분화적조공급기재결장암발생발전중적작용。방법응용신호전도여전록격활인자4기인고제( STAT4-/-)소서건립염증상관장암모형,STAT4-/-소서통과복강주사양화우담갑완( AOM)화음용함DSS수유발급성장염,건립염증상관결장종류모형병감정；응용류식세포기술분석STAT4기인결실대면역세포아군분화화동원적영향。결과 STAT4-/-소서표현위명현적결장종류병변,이야생형( WT )대조조재결장적중하단화항문처지유염성병변화상피조직증생；CD11b﹢Gr-1﹢MDSCs재 STAT4-/-소서적외주혈、비장화골수내적백분솔교 WT 대조조소서현저증가( P ＜0.05)。결론 STAT4결실능촉진소서결장종류적발생,기궤제가능여STAT4신호통로억제도치CD11b﹢Gr-1﹢MDSCs적이상분화화동원유관。
Objective To investigate the role of signal transducer and activator of transcription 4 ( STAT4 ) signal pathway in the migration of Myeloid-derived suppressor cells ( MDSCs) and in inflammation associated carcinogenesis. Methods The inflammation associated colon cancer mouse model was established with STAT4 genetic deficiency mice through administration of azoxymethane ( AOM) and dextran sulfate sodium ( DSS) treatment. Flow cytometery was performed to analyze the expression of CD11b﹢Gr-1﹢MDSCs in the peripheral blood,spleen,and bone marrow. Results Genetic deficiency of STAT4 showed colon tumorigenesis following AOM/DSS treatment. Significant increasing of CD11b﹢Gr-1﹢MDSCs was examined in the inflamed colon tissue and in the peripheral blood of STAT4 -/ - mice. Genetic deficiency of STAT4 promoted the proliferation and differentiation of CD11b﹢Gr-1﹢immature myeloid cells within bone marrow and spleen res-ervoirs. Conclusions STAT4 signal pathway plays a criticle role in regulating the differentiation and migration of CD11b﹢Gr-1﹢MDSCs that promotes inflammation associated colonic tumorigenesis.