TY -的T1 -间充质基质细胞(干细胞)(MSC)治疗调节mir - 193 b - 5 - p的表达减弱sepsis-induced急性肺损伤JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.04216 -2020欧元SP - 2004216 AU -多斯桑托斯,克劳迪娅c . AU - Amatullah Hajera盟——Vaswani是m . AU - Maron-GutierrezTatiana AU -金,迈克尔AU -梅,雪莉H.J.盟——Szaszi Katalin AU -蒙泰罗,安娜保拉·t . AU - Varkouhi Amir k . AU - Herreroz拉奎尔AU - Lorente,何塞天使AU - Tsoporis,詹姆斯·n . AU -古普塔Sahil聊友,Ektesabi阿明盟——Kavantzas Nikolaos盟——Salpeas Vasileios AU -马歇尔,约翰·c·AU -罗科,帕特里夏·r·m . AU -马斯登,菲利普·a . AU -维斯,Daniel j . AU -斯图尔特,邓肯•j . AU -胡Pingzhao AU - Liles说,w·康拉德Y1 - 2021/01/01 UR - //www.qdcxjkg.com/content/early/2021/05/28/13993003.04216 - 2020. -抽象N2 -尽管间充质基质细胞(干细胞)(MSC)政府变弱sepsis-induced肺损伤在临床前模型中,其作用机制和宿主免疫系统对其治疗效果的贡献尚不清楚。我们发现，在脓毒症小鼠肺中，MSCs降低了宿主源microRNA (miR)-193b-5p的表达，并增加了其靶基因紧密连接蛋白occludin (Ocln)的表达。突变Ocln 3 ' UTR miR-193b-5p结合序列可使其与Ocln mRNA的结合受损。在人原发性肺微血管内皮细胞(HPMECs)中抑制miR-193b-5p可防止肿瘤坏死因子(TNF)诱导的Ocln基因和蛋白表达减少和屏障功能丧失。MSC条件培养基可减轻tnf诱导的miR-193b-5p的上调和Ocln的下调。在体内给药时，MSC条件培养基重现了MSC给药对肺miR-193b-5p和Ocln表达的影响。MiR-193b缺陷小鼠对LPS灌注诱导的肺部炎症和损伤具有抗性。 Silencing of Ocln in miR-193b deficient mice partially recovered the susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the finding of increased miR-193b-5p expression levels in lung autopsy samples from Acute Respiratory Distress Syndrome patients who died with diffuse alveolar damage.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. dos Santos has nothing to disclose.Conflict of interest: Dr. Amatullah has nothing to disclose.Conflict of interest: Dr. Vaswani has nothing to disclose.Conflict of interest: Dr. Maron-Gutierrez has nothing to disclose.Conflict of interest: Mr. Kim has nothing to disclose.Conflict of interest: Dr. Mei has nothing to disclose.Conflict of interest: Dr. Szaszi has nothing to disclose.Conflict of interest: Dr. Teixeira Monteiro has nothing to disclose.Conflict of interest: Dr. Varkouhi has nothing to disclose.Conflict of interest: Dr. Herrero has nothing to disclose.Conflict of interest: Dr. Lorente has nothing to disclose.Conflict of interest: Dr. Tsoporis has nothing to disclose.Conflict of interest: Dr. Gupta has nothing to disclose.Conflict of interest: Dr. Ektesabi has nothing to disclose.Conflict of interest: Dr. Kavantzas has nothing to disclose.Conflict of interest: Dr. Salpeas has nothing to disclose.Conflict of interest: Dr. Marshall reports personal fees from AM Pharma, personal fees from Gilead Pharmaceuticals, outside the submitted work.Conflict of interest: Dr. Rocco has nothing to disclose.Conflict of interest: Dr. Marsden has nothing to disclose.Conflict of interest: Dr. Weiss has nothing to disclose.Conflict of interest: Dr. Stewart reports other from Northern Therapeutics, outside the submitted work.Conflict of interest: Dr. Hu has nothing to disclose.Conflict of interest: Dr. Liles has nothing to disclose. ER -