Lu Ying-ying, Yang Xian, Chen Wen-qing, Ju Zhen-yu, Shou Zhang-fei, Jin Juan, Zhang Xiao-hui, Chen Jiang-hua, Jiang Hong
Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Institute of Aging Research and Max-Planck-Research Group on Stem Cell Aging, Hangzhou Normal University, Hangzhou 311121, China.
J Zhejiang Univ Sci B. 2014 Jun;15(6):566-74. doi: 10.1631/jzus.B1300115.
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-1α (EF-1α), 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.
衰老为肾脏疾病的促成风险因素之一。越来越多的证据支持这样一种观点，即肾组织细胞中的端粒长度是机体衰老的一个指标。先前确定的衰老标志物（与cathelin相关的抗菌肽（CRAMP）、微管相关蛋白、延伸因子-1α（EF-1α）和几丁质酶）不仅与小鼠端粒驱动的衰老有关，而且与人类衰老和慢性疾病有关。本研究聚焦于中国人群中这些生物标志物与IgA肾病（IgAN）进展之间的关系。对于260名个体，使用直接酶联免疫吸附测定（ELISA）和免疫荧光染色在盲法数据集中测定这四种标志物。在人类IgAN进展过程中，血浆、尿液和肾组织中CRAMP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），随着端粒缩短并没有蛋白质上调。此外,CRAMP和几丁质酶的组合能够以88.2%/92.5%（血浆）和74.3%/84.2%（尿液）的灵敏度/特异性区分IgAN患者与健康个体。这些数据提供了实验证据，表明端粒缩短和相关炎症蛋白与人类IgAN有关，这可能是该疾病进展研究的一个新方向。
