LncRNA XIST在低氧培养BM-MSCs来源Exosomes治疗急性肺损伤中的作用和机制研究

急性肺损伤（ALI）发病急、死亡率高，尚缺乏有效治疗手段。BM-MSCs回输可以有效治疗ALI，但机制不清；课题组已发表的研究发现BM-MSCs，尤其是低氧培养BM-MSCs，可以通过上调肺泡上皮细胞Claudin-4蛋白的表达，发挥保护肺上皮细胞屏障的作用，并进一步研究发现BM-MSCs分泌Exosomes中高表达的lncRNA XIST可能通过调控miR-455-3p介导了这一作用。本研究拟在前期研究上，利用超高速离心、慢病毒质粒转染和芯片等各种技术，在体内外ALI模型中证实低氧BM-MSCs来源Exosomes可以保护肺上皮屏障功能，并明确XIST在上调Claudin-4保护肺损伤的作用；结合Luciferase等技术，揭示XIST是通过吸附miR-455-3p从而上调Claudin-4。研究成果将揭示低氧BM-MSCs改善ALI肺脏功能的机制，并可望为ALI治疗提供全新方法。

Acute lung injury (ALI) is a disease with high incidence and high mortality. Currently, there is still a lack of effective treatment. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transfusion could be effective in the treatment of ALI. Our previous published study reveal that BM-MSCs played a protective effect of pulmonary epithelial cell barrier through upregulating claudin-4 expression of alveolar epithelial cells. And further study indicated the long non-coding RNA XIST high expressed in BM-MSCs derived exosomes may mediate the effect of BM-MSCs on Claudin-4 expression. This study intends to verify exosomes derived from BM-MSCs could protect lung epithelial barrier function and explicit the role of XIST in this process in vitro/vivo ALI model through different methods, such as ultra high speed centrifugation, chronic virus plasmid transfection and chip technology. Furthermore, this study will also explore the mechanism how XIST regulates Claudin-4 expression through miRNA array and CHIRP. The results of this study will further reveal the mechanism how BM-MSC protect lung function in ALI, provide a new therapeutic method for the clinical treatment of acute lung injury though BM-MSC secreted Exosomes and offer a new therapeutic target for ALI.