激活SLFN4 MDSCs以加速胃黏膜肠化生。
activates SLFN4MDSCs to accelerate gastric intestinal metaplasia.
作者信息
Zhao Zhihong, Liu Rui, Peng Ye, Li Cun, Li Qian
机构信息
Xiangya Hospital Central South University, 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China.
Hospital of China University of Geosciences, No.388 Lumo Road, Hongshan District, Wuhan, Hubei 430074, China.
出版信息
iScience. 2024 Oct 28;27(11):111255. doi: 10.1016/j.isci.2024.111255. eCollection 2024 Nov 15.
Chronic infection with () is a major risk factor for gastric cancer. This work attempted to investigate the underlying mechanism of SLFN4 myeloid-derived suppressor cells (MDSCs) in affecting gastric intestinal metaplasia (GIM). infection enhanced the expression of IFN-α and SLFN4, and activated JAK2/STAT1 signaling pathway in bone marrow cells or mouse gastric corpus. Meanwhile, IFN-α induced the transportation of STAT1 to the nucleus and activated the SLFN4 promoter. Moreover, the proportion of SLFN4MDSC was decreased in IFN-α-treated bone marrow cells following TB42 treatment (JAK2/STAT1 signaling inhibitor). Additionally, miR-130b-3p was secreted by SLFN4MDSCs. MiR-130b-3p was upregulated, tuberous sclerosis complex 1 (TSC1) was downregulated in patients. MiR-130b-3p inhibition in SLFN4MDSCs alleviated GIM. In conclusion, infection-induced high levels of IFN-α activated JAK/STAT1 signaling pathway to promote differentiation of SLFN4MDSCs. High expression of miR-130b-3p in SLFN4MDSCs inactivated Shh signaling pathway by targeting TSC1, thereby promoting GIM.
（某种病菌）慢性感染是胃癌的主要危险因素。这项研究试图探究SLFN4髓源性抑制细胞（MDSCs）影响胃黏膜肠化生（GIM）的潜在机制。（某种病菌）感染增强了IFN-α和SLFN4的表达，并激活了骨髓细胞或小鼠胃体中的JAK2/STAT1信号通路。同时，IFN-α诱导STAT1转运至细胞核并激活SLFN4启动子。此外，用TB42（JAK2/STAT1信号抑制剂）处理后，经IFN-α处理的骨髓细胞中SLFN4 MDSC的比例降低。另外，miR-130b-3p由SLFN4 MDSCs分泌。在（某种病菌）感染患者中，miR-130b-3p上调，结节性硬化复合物1（TSC1）下调。抑制SLFN4 MDSCs中的miR-130b-3p可减轻胃黏膜肠化生。总之，（某种病菌）感染诱导的高水平IFN-α激活JAK/STAT1信号通路，以促进SLFN4 MDSCs的分化。SLFN4 MDSCs中miR-130b-3p的高表达通过靶向TSC1使Shh信号通路失活，从而促进胃黏膜肠化生。
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