肾脏纤维化是多种慢性肾脏疾病（CKD）进展到终末期肾病的共同病理基础。NEK7属于NEK蛋白激酶家族，在细胞增殖过程中起重要作用。近期研究又显示NEK7可能是NLRP3炎症小体的新组分，参与炎症小体活化，但NEK7在肾脏疾病中的作用尚无研究。在线生物数据库分析发现NEK7在CKD患者肾脏高表达。预实验也显示在UUO模型及TGF-β1刺激的肾小管上皮细胞及肾间质成纤维细胞，NEK7与NLRP3同时上调。干扰NEK7可下调NLRP3并减少细胞外基质。生物信息学分析显示转录因子ASH1与NEK7启动子区有9个结合位点，且TGF-β1可上调ASH1，而敲低ASH1可下调NEK7。由此推测：转录因子ASH1启动NEK7表达，进而通过调控NLRP3炎症小体和/或细胞增殖介导肾小管间质纤维化。本课题将在整体、细胞和分子层面探讨NEK7调控肾小管间质纤维化的作用及机制，为防治CKD提供新思路。

Renal fibrosis is the common pathological features of various chronic renal diseases, which contributes to the progression of CKD to end-stage renal disease. NEK7, a member of NIMA-related kinase (Nek) family, plays an important role in the process of cell proliferation. As a recently identified possible component of NLRP3 inflammasome, NEK7 is involved in the activation of NLRP3 inflammasome. However, the role of NEK7 in renal disease is unclear. Analysis from an online biological database revealed that NEK7 was higher in the kidneys of CKD patients. Our preliminary study also showed that the expression of NEK7 and NLRP3 were all upregulated in UUO mouse model and TGF-β1-treated renal tubular epithelial cells and renal interstitial fibroblasts. Moreover, the expression of NLRP3 and the extracellular matrix level were decreased when NEK7 was inhibited by a siRNA approach, indicating a potential role of NEK7 in activating the NLRP3 inflammasome and promoting the fibrotic response in kidney. Bioinformatic analysis indicated that there were nine binding sites of the transcription factor ASH1 on the promoter region of NEK7. Furthermore, ASH1 was induced by TGF-β1 in RTECs and silencing ASH1 reduced NEK7 expression. Therefore, we hypothesized that ASH1-regulated NEK7 could contribute to the pathogenesis of renal tubulointerstitial fibrosis through activating NLRP3 inflammasome and/or modulating cell cycle progression and cell proliferation. In the current proposal, we will employ CKD patients’ samples and models of animals, cells, and molecules to define the role of NEK7 in modulating renal tubulointerstitial fibrosis, as well as the underlying mechanisms, which could bring the new insights into the understanding and intervention of CKD.