肾结石是泌尿外科的常见病，人群发病率高。目前肾结石形成机制尚不明确，既往研究证实肾乳头处Randall斑是结石形成的起始点。申请人前期研究发现高浓度钙离子可以刺激肾乳头中的肾间质成纤维细胞（hRIFs）发生类成骨转化，产生钙盐沉积。通过基因芯片技术，申请人筛选出Randall斑与正常组织中存在差异表达的基因LncRNA RPLnc1，并通过RNA-pulldown、RNA-seq，进一步筛选出可能与其相互作用的蛋白MSX2。并提出假设：高浓度钙离子可刺激hRIFs中Lnc RPLnc1表达升高，Lnc RPLnc1可通过调控MSX2表达，进而促进hRIFs发生类成骨转化产生钙盐沉积，形成Randall斑。本项目拟通过RIP、CHIP、Luciferase等方法，从细胞、动物模型、临床标本等多个层面进一步证实上述猜想。研究将为肾结石的治疗和预防提供新的思路和治疗靶点。

Renal calculi are common disease in urology, with high incidence. At present, the mechanism of renal calculi formation is not clear. Previous studies have confirmed that Randall’s Plaques at the renal papilla is the starting point of stone formation. In the applicant's previous study, it was found that the osteogenic-like differentiation of human renal interstitial fibroblasts (hRIFs) stimulated by high concentration of calcium ions might be involved in the formation of stones. Through gene chip technology, the applicant screened the differentially expressed gene LncRNA RPLnc1 in Randall’s Plaques tissue, and further screened the proteins MSX2 that may interact with it through RNA-pulldown and RNA-seq. The hypothesis is that high concentration of calcium can stimulate the expression of LncRNA RPLnc1 in hRIFs, and LncRNA RPLnc1 can regulate the expression of MSX2, thus promoting the osteogenic-like differentiation of hRIFs, then forming the Randall’s Plaques. In this project, RIP、CHIP、Luciferase and other methods are used to further confirm the above conjecture from cell, animal model and clinical specimen. The research will provide new ideas and target genes for the treatment and prevention of renal calculi.