Proteins induced by telomere dysfunction are associated with human IgA nephropathy
Proteins induced by telomere dysfunction are associated with human IgA nephropathy
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DOI：
10.1631/jzus.b1300115
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发表时间：
2014-06-01
影响因子：
5.1
通讯作者：
Jiang, Hong
中科院分区：
文献类型：
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作者：
Lu, Ying-ying;Yang, Xian;Jiang, Hong
衰老是肾脏疾病的危险因素之一。越来越多的证据表明，肾脏组织细胞的端粒长度是机体衰老的一个指标。先前发现的衰老标志物（cathelin-related antimicrobial peptide， CRAMP）、stathmin、伸长因子-1 α（伸长因子-1 α）和几丁质酶)不仅与小鼠端粒驱动的衰老有关，还与人类衰老和慢性疾病有关。本研究的重点是这些生物标志物与中国人群IgA肾病（IgAN）进展之间的关系。对于260个个体，使用直接酶联免疫吸附试验（ELISA）和免疫荧光染色在盲数据集中确定了这四种标记物。在IgAN进展过程中，血浆、尿液和肾脏组织中camp和几丁质酶的表达水平升高。而对于其他肾病，如系统性红斑狼疮（SLE）、糖尿病肾病（DN）和局灶节段性肾小球硬化（FSGS），没有蛋白上调与端粒缩短。此外，结合CRAMP和几丁质酶可以区分IgAN患者与健康个体，其敏感性/特异性分别为88.2%/92.5%（血浆）和74.3%/84.2%（尿液）。这些数据提供了端粒缩短及相关炎症蛋白与人类IgAN相关的实验证据，可能为疾病进展研究提供新的方向。
Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers (cathelin-related antimicrobial peptide (CRAMP), stathmin, elongation factor-1 alpha (EF-1 alpha), and chitinase) were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy (IgAN) progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus (SLE), diabetic nephropathy (DN), and focal segmental glomerulosclerosis (FSGS), there is no protein upregulation with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% (plasma) and 74.3%/84.2% (urine) sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.