巨噬细胞半乳糖型凝集素1通过抑制NF-κB信号通路延缓炎症诱导的小鼠造血干细胞分化  

Macrophage galactose-type lectin 1 limits mouse hematopoietic stem cell differentiation in context of inflammation by inhibiting NF-κB signaling pathway

作　　者：李漫纯 詹蔷 邹密 白可 易微微 鞠振宇 陈陟阳 LI Manchun;ZHAN Qiang;ZOU Mi;BAI Ke;YI Weiwei;JU Zhenyu;CHEN Zhi-yang(Key Laboratory of Regenerative Medicine of Ministry of Education,Department of Developmental&Regenerative Medicine,College of Life Science and Technology,Jinan University,Guangzhou 510632,China)

机构地区：[1]暨南大学教育部再生医学重点实验室,暨南大学发育与再生医学系,生命科学技术学院,广东广州510632

出　　处：《中国病理生理杂志》2025年第4期679-687,共9页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年项目(No.32300663);广东省自然科学基金面上项目(No.2022A1515011204)。

摘　　要：目的:探讨巨噬细胞半乳糖型凝集素1(macrophage galactose-type lectin 1,Mgl1)基因缺失在小鼠造血干细胞稳态和炎症条件下的作用和机制。方法:实验分为对照组(野生型小鼠)和实验组(Mgl1基因敲除小鼠)。采用流式细胞术分析两组小鼠的外周血和骨髓中各类血液细胞的百分率,探究Mgl1基因缺失对小鼠稳态造血的影响,每组3~4只小鼠;利用体内骨髓移植和体外甲基纤维素细胞集落形成实验,评估Mgl1基因缺失对小鼠造血干/祖细胞的造血系统重建能力和集落形成能力的影响,每组5只小鼠;选用脂多糖(lipopolysaccharide,LPS)诱导的炎症模型,在体内和体外探究Mgl1基因缺失对小鼠造血干/祖细胞炎症反应应答的影响,每组5~8只小鼠;利用Western blot法和RT-qPCR解析Mgl1调节小鼠造血干/祖细胞炎症反应应答的分子机制,每组3只小鼠。结果:(1)Mgl1基因缺失不影响小鼠稳态造血干/祖细胞数目(P>0.05)。(2)在体外炎症刺激模型中,Mgl1基因缺失促进LPS诱导的小鼠造血干/祖细胞分化(P<0.01)。(3)在体内炎症模型中,Mgl1基因缺失促进炎症刺激诱导的小鼠造血干细胞数目耗竭(P<0.01)。(4)Mgl1通过NF-κB信号通路调控小鼠造血干/祖细胞的炎症应答(P<0.01)。结论:Mgl1通过NF-κB信号通路调控小鼠造血干细胞的炎症反应。AIM:To investigate the effects of macrophage galactose-type lectin 1(Mgl1)gene deletion on hematopoietic stem/progenitor cells(HSPCs)under steady-state conditions and inflammation.METHODS:Mice were divided into a control group(wild-type)and an experimental group(Mgl1 gene-deleted).Flow cytometry was used to analyze the proportions of various hematopoietic cell lineages in the peripheral blood and bone marrow of both groups,assessing the impact of Mgl1 gene deletion on steady-state hematopoiesis(n=3~4).Transplantation and colony-forming assays were utilized to evaluate the effects of Mgl1 gene deletion onthe repopulation capacity and colony-forming ability of HSPCs(n=5).The LPS-induced inflammation model was employed to examine the effects of Mgl1 gene deletion on the inflammatory response of HSPCs both in vitro and in vivo(n=5~8).Western blot and RT-qPCR were conducted to analyze the alterations in signaling pathways regulated by Mgl1 in the inflammatory response of HSPCs(n=3).RESULTS:(1)Mgl1 gene deletion had no significant effecton steady-state hematopoiesis(P>0.05).(2)Mgl1 gene deletion promoted inflammation-induced cell differentiation of HSPCs(P<0.01).(3)Mgl1 gene deletion accelerated the exhaustion of HSPCs under prolonged inflammatory conditions(P<0.01).(4)Mgl1 was found to regulate the inflammatory response of HSPCs via the NF-κB signaling pathway.CONCLUSION:Mgl1 gene deletion enhances the inflammatory response of HSPCs via the NF-κB signaling pathway.

关 键 词：巨噬细胞半乳糖型凝集素1 造血干细胞 炎症 NF-ΚB信号通路 

分 类 号：R551[医药卫生—血液循环系统疾病] R329.28[医药卫生—内科学] R363[医药卫生—临床医学]