IgA肾病（IgAN）是儿童最常见的原发性肾小球疾病之一。既往认为儿童期起病者预后良好，但随访20年，约30％进入终末期肾病。目前尚无特异性有效延缓其进展的手段。已知炎症和纤维化是其发病和进展的重要环节。近年发现长链非编码RNA（LncRNA）是炎症和纤维化网络信号中新的调控分子，其在儿童IgAN中的作用值得研究。我们前期从IgAN患儿肾组织中筛选出特异性表达的LncRNA163，并证实其可桥联GLI2和CDK9促进UUO小鼠肾间质纤维化。基于前期研究推测：LncRNA163可能通过桥联炎症和纤维化信号促进儿童IgAN进展。本项目拟通过IgAN小鼠、LncRNA163基因敲除小鼠及LncRNA163特异性阻断剂锁核酸LNA-163探讨LncRNA163的功能；通过体内外实验进一步研究其桥联GLI2和CDK9的分子机制，为儿童IgAN的进展机制提供新思路，为早期精准防治提供潜在的新靶点。

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis in children. For children with IgAN, the long-term prognosis was believed benign. However, recent studies demonstrated that 30% of children with IgAN developed into end-stage renal disease after 20 years of onset. Currently we lack the specific treatments to delay the progression of IgAN, making this unmet clinical need. It is believed that inflammation and fibrosis are the two major determinants in the development and progression of IgAN. Recently studies demonstrated that long non-coding RNA (LncRNA) is a novel active regulator in the inflammatory and fibrotic networks. The role of LncRNA in the pathogenesis of childhood IgAN is worth exploring. We identified LncRNA163 through performing a microarray analysis and bioinformatics screen of LncRNA expressed in biopsy tissue from children with IgAN. Our LncRNA163 deficient mice were protected from renal interstitial fibrosis in model of unilateral ureteral obstruction (UUO). Further, administration of LNA163 into mice with UUO inhibited the expression of LncRNA163 and suppressed renal interstitial fibrosis. Finally our in vitro study demonstrated that knockdown of LncRNA163 by LNA163 significantly reduced pIgA1-induced fibrotic response in human mesangial cells while biotinylated sense LncRNA163 bridges GLI2 and CDK9. Based on our strong preliminary data, we hypothesize that LncRNA163 plays its central role in the development and progression of childhood IgAN. The functional role of LncRNA163 will be determined by genetic (LncRNA163 knockout mice) and pharmacologic (LNA163) approaches in our recently established moue model of IgAN. We will also perform mechanistic studies to explore how LncRNA163 integrates inflammatory and fibrotic signalling pathways to promote fibrosis through bridging GLI2 and CDK9. This study presents a novel mechanism for the pathogenesis of IgAN and provides a potential new therapeutic target for childhood IgAN.