炎性巨噬细胞M1持续性聚集、释放炎性介质并诱导炎症反应和组织损伤是急性肾损伤（AKI）进展的重要因素。我们前期数据显示，长链非编码RNA9884（LRNA9884）在小鼠AKI模型的肾脏中表达明显升高；骨髓来源巨噬细胞中LRNA9884的表达可以被炎症刺激诱导；下调LRNA9884能减少巨噬细胞的表面膜蛋白C型凝集素Mincle的表达，从而减少M1巨噬细胞聚集。据此我们认为，LRNA9884是一促进AKI的关键调控因素，它上调巨噬细胞的Mincle蛋白，维持M1巨噬细胞表型持续促进炎症释放。本课题拟用AKI小鼠模型结合体外培养骨髓来源巨噬细胞，1）明确AKI模型中，LRNA9884的表达变化及与巨噬细胞的相关性。2）细胞层面揭示LRNA9884在巨噬细胞中的生物学功能。3）基因层面阐明LRNA9884在巨噬细胞中对与Mincle的调控机制。本研究拟进一步为AKI的治疗提供新的靶点。

Macrophages are key inflammatory cells that play a critical role in renal inflammation and repair after acute kidney injury (AKI). In our previous study, we found 1) Novel lncRNA_9884 (LRNA9884) was highly expressed in cisplatin-induced AKI kidney; 2) The expression of LRNA9884 was largely upregulated by TNF-α stimulation in bone marrow–derived macrophages (BMDMs); 3) Knockdown of LRNA9884 in BMDMs inhibited the expression of Mincle, which is a specific macrophage receptor induced on the cytomembrane and is responsible for maintaining inflammatory phenotypes of M1 macrophages during the progress of AKI. Hereby, we put forward to the hypothesis that LRNA9884 promotes the inflammatory response via enhancing Mincle-dependent M1 macrophage phenotype maintenance after AKI injury. In the proposed study, we would employ two mouse AKI models including cisplatin-induced and ischemia reperfusion-induced models, and fully utilize cultured BMDMs by using multiple molecular biological techniques to 1) Validate the relationship between LRNA9884 expression and macrophage polarization in AKI; 2) Uncover the biological function of LRNA9884 in macrophage polarization and function; 3) Uncover the molecular mechanism by which LRNA9884 regulates Mincle in vivo and in vitro. This study will shed new lights on the understanding of pathological role of novel LRNA9884 in AKI.