IgA肾病是我国最常见的慢性肾脏疾病，是导致我国尿毒症的最主要病因，但其确切发生机制仍不清楚。申请人前期研究发现由端粒缺陷诱发细胞衰老分泌的一组特异性蛋白质。这组蛋白质不仅能很好的预示人类衰老，还能够预示慢性疾病的发生发展，如肝脏纤维化、骨髓增生异常综合征、IgA肾病等。进一步研究后从这一组蛋白质中锁定了与肾脏疾病特异性相关的一个关键蛋白质LL37，并发现端粒缺陷可能通过诱发分泌的特异性蛋白质LL37与炎症细胞相互作用从而影响到IgA肾病的进展。揭示了端粒缺陷触发衰老的同时，可能协同启动了炎症细胞对人体组织器官的靶向免疫作用，导致了IgA肾病的发生发展。本研究通过IgA肾病的端粒触发炎症细胞捕获机制的深入研究，阐明IgA肾病发病的分子机制，为延缓疾病的进程，诊断和治疗疾病找到新的靶点。

The applicant has been engaged in the research of the role of telomere shortening disfunction in human aging and chronic disease processes since 2005, and first discovereda group of specific proteins secreted by senescent cellswhich was induced by telomere defects.This group of proteins is not only a good predictor of human aging , but also predicts the development of chronic diseases , such as liver fibrosis, myelodysplasticsyndroms (MDS) and IgA nephropathy. Further study focused on a specific protein named LL37,which is associated with kidney diseasespecifically. Researches found that telomere defects may induce the interact between the proteins and inflammatory cells, and affect the progress of severe IgA nephropathy. Evidences showed that telomere dysfunction could induces aging, as well as activate the targeted immune function of inflammatory cells to the human tissues and organs, leading to the development of related diseases. The applicantpublished these research results in papers of PNAS as the first author , Nature Medcine the second , and Cell the fourth. Based on all above, the applicantwill do further research to study the mechanism of inflammatory cells capture triggered by telomere in IgA nephropathy, and find new targetsto slow the progression of the disease, provide diagnosis and treatment of disease.