摘要
背景:大量研究表明间充质干细胞能够通过多种免疫调节途径治疗自身免疫性疾病,基因修饰可能提高间充质干细胞的治疗潜力。miR-1-5p在系统性红斑狼疮中呈低表达,过表达miR-1-5p的间充质干细胞可能对系统性红斑狼疮具有治疗作用。目的:探讨miR-1-5p修饰的脐带间充质干细胞是否介导JAK2/STAT3通路对系统性红斑狼疮MRL/lpr模型小鼠存在治疗作用。方法:将20只MRL/lpr狼疮小鼠随机分为miR-1-5p转染脐带间充质干细胞治疗组(UC-MSCs+miR-1-5p组)、miRNA阴性对照转染脐带间充质干细胞治疗组(UC-MSCs+miR-NC组)、脐带间充质干细胞治疗组(UC-MSCs组)、PBS治疗组(PBS组)、MRL/lpr狼疮小鼠未处理组(对照组)。以尾静脉移植的方式治疗MRL/lpr狼疮小鼠,每周1次,治疗5次。结束治疗后间隔1周处死小鼠,苏木精-伊红染色观察各组MRL/lpr小鼠肝组织和肠组织的病理变化;Western blot法检测各组小鼠肾组织JAK2/STAT3通路蛋白及其磷酸化水平和白细胞介素18的表达水平。结果与结论:(1)与对照组相比,UC-MSCs+miR-1-5p组、UC-MSCs+miR-NC组和UC-MSCs组MRL/lpr小鼠肝组织中炎性细胞浸润明显减少,UCMSCs+miR-NC组可见肝细胞水肿变性;UC-MSCs+miR-1-5p组MRL/lpr小鼠肠组织中杯状细胞明显增多,其余各组差异不显著。(2)与对照组相比,UC-MSCs+miR-1-5p组狼疮小鼠肾组织中p-JAK2(Y1007+Y1008)、p-STAT3(s727)、白细胞介素18的表达水平显著下调(P <0.05);UC-MSCs组狼疮小鼠肾组织中p-STAT3(s727)(P <0.05)、白细胞介素18 (P <0.01)显著下调;UC-MSCs+miR-NC组白细胞介素18的表达水平显著下调(P <0.05);各组狼疮小鼠肾组织中p-STAT3(Y705)的表达差异无显著性意义(P> 0.05)。与PBS组相比,UC-MSCs组白细胞介素18表达明显下调(P <0.05)。(3)结果表明,miR-1-5p修饰的脐带间充质干细胞可能通过抑制JAK2/STAT3通路的激活和白细胞介素18的表达来缓解MRL/lpr小鼠肝肠损害,从而对狼疮小鼠起
BACKGROUND:Numerous studies have shown that mesenchymal stem cells can treat autoimmune diseases through a variety of immunomodulatory pathways,and genetic modification may improve the therapeutic potential of mesenchymal stem cells.MiR-1-5p is lowly expressed in systemic lupus erythematosus,and mesenchymal stem cells overexpressing miR-1-5p may have a therapeutic effect on systemic lupus erythematosus.OBJECTIVE:To investigate whether miR-1-5p-modified umbilical cord mesenchymal stem cells mediate the JAK2/STAT3 pathway and have a therapeutic effect on systemic lupus erythematosus MRL/lpr model mice.METHODS:Twenty MRL/lpr lupus mice were randomly divided into miR-1-5p transfected umbilical cord mesenchymal stem cells treatment group(UCMSCs+miR-1-5p group),miRNA negative control transfected umbilical cord mesenchymal stem cells treatment group(UC-MSCs+miR-NC group),umbilical cord mesenchymal stem cell treatment group(UC-MSCs group),PBS treatment group(PBS group),and MRL/lpr lupus mice untreated(control group).MRL/lpr lupus mice were treated with tail vein transplantation,once a week,5 times.Mice were sacrificed at 1-week intervals after the end of treatment.Hematoxylin-eosin staining was used to observe the pathological changes of liver tissue and intestinal tissue of MRL/lpr mice in each group.Western blot assay was used to detect JAK2/STAT3 pathway proteins and their phosphorylation levels and expression levels of interleukin-18 in kidney tissue of mice in each group.RESULTS AND CONCLUSION:(1) Compared with control group,the infiltration of inflammatory cells in liver tissue of MRL/lpr mice in UC-MSCs+miR-1-5p group,UC-MSCs+miR-NC group,and UC-MSCs group decreased significantly,and hepatocyte edema and degeneration could be seen in UC-MSCs+miR-NC group.Goblet cells in intestinal tissue of MRL/lpr mice in UC-MSCs+miR-1-5p group increased significantly,but there was no significant difference among other groups.(2) Compared with control group,the expression of p-JAK2(Y1007+Y1008),p-STAT3(s727) and interleukin-18 in
作者
丁丽丽
胡明智
武志慧
孙晓林
王永福
Ding Lili;Hu Mingzhi;Wu Zhihui;Sun Xiaolin;Wang Yongfu(Department of Rheumatology and Immunology,First Affiliated Hospital of Baotou Medical College,Baotou 014010,Inner Mongolia Autonomous Region,China;Central Laboratory(Key Laboratory of Autoimmunity in Inner Mongolia Autonomous Region),First Affiliated Hospital of Baotou Medical College,Baotou 014010,Inner Mongolia Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2023年第10期1492-1500,共9页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(81860294),项目负责人:孙晓林
内蒙古自治区自然科学基金项目(2019MS08055),项目参与人:孙晓林
内蒙古自治区自然科学基金项目(2021MS08045),项目负责人:孙晓林
内蒙古自治区科技计划项目(201802089),项目参与人:孙晓林
内蒙古自治区科技计划项目(2019GG052),项目负责人:王永福。
