DCR2, a Cellular Senescent Molecule, Is a Novel Marker for Assessing Tubulointerstitial Fibrosis in Patients with Immunoglobulin A Nephropathy
DCR2, a Cellular Senescent Molecule, Is a Novel Marker for Assessing Tubulointerstitial Fibrosis in Patients with Immunoglobulin A Nephropathy
复制标题
DCR2 是一种细胞衰老分子，是评估免疫球蛋白 A 肾病患者肾小管间质纤维化的新标志物
DOI：
10.1159/000502233
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发表时间：
2019-10-01
影响因子：
2.8
通讯作者：
He, Yani
中科院分区：
文献类型：
--
作者：
Chen, Jia;Hu, Wei;He, Yani
背景/目标：应激诱导的细胞衰老导致细胞周期停滞，与年龄无关，在慢性肾脏病（CKD）进展中起重要作用。DcR 2作为一种衰老标志物，仅在衰老的肾小管上皮细胞中表达。本研究的目的是检测尿DcR 2（uDcR 2）是否可以作为免疫球蛋白A肾病（IgAN）患者肾小管间质纤维化（TIF）的潜在生物标志物。方法：采用酶联免疫吸附法（ELISA）检测210例IgAN患者和80例健康志愿者血清uDcR 2水平。我们研究了uDcR 2/Cr水平、肾功能和病理参数之间的关系，使用回归分析来识别TIF的风险因素，并使用曲线下面积（AUC）方法来预测TIF。肾DcR 2表达通过免疫组织化学定量。通过共聚焦显微镜分析DcR 2与纤维化标志物（α-平滑肌肌动蛋白[α-SMA]，胶原蛋白III）的共表达。结果：IgAN患者和重度TIF患者的uDcR 2/Cr水平显著高于健康对照组。各组间血清DcR 2水平相似。在uDcR 2/Cr 201 ng/g的患者中，1-2期CKD和T0的IgAN患者比例最高，其中4-5期CKD和T2。uDcR 2/Cr水平与尿白蛋白/肌酐比值（ACR）、尿N-乙酰-β-D-氨基葡萄糖苷酶（uNAG）/Cr和TIF评分呈正相关，与估计肾小球滤过率（eGFR）呈负相关。uDcR 2/Cr、uNAG、ACR和eGFR是TIF的独立预测因子，uDcR 2/Cr的AUC为0.907。该AUC值高于eGFR、uNAG/Cr或ACR的观察值。uDcR 2/Cr预测TIF的敏感性为87.0%，特异性为80.5%。此外，uDcR 2/Cr水平与肾脏DcR 2表达百分比呈正相关。肾DcR 2与IgAN患者肾脏中的α-SMA和胶原III共定位。结论：uDcR 2/Cr水平与TIF的严重程度及肾功能指标密切相关。uDcR 2/Cr是预测IgAN患者TIF的潜在生物标志物。
Background/Aims: Stress-induced cell senescence, which contributes to cell cycle arrest and is independent of age, plays an important role in chronic kidney disease (CKD) progression. DcR2, as a senescent marker, exclusively expressed in senescent tubular epithelia. The objective of this study was to examine whether urinary DcR2 (uDcR2) could be a potential biomarker for tubulointerstitial fibrosis (TIF) in patients with immunoglobulin A nephropathy (IgAN). Methods: This study included 210 IgAN patients and 80 healthy volunteers, with uDcR2 levels measured using enzyme-linked immunosorbent assay. We examined the relationship among uDcR2/Cr levels, renal function, and pathological parameters, using regression analysis to identify risk factors for TIF and the area under the curve (AUC) approach to predict TIF. Renal DcR2 expression was quantified by immunohistochemistry. Co-expression of DcR2 with fibrotic markers (alpha-smooth muscle actin [alpha-SMA], collagen III) was analyzed by confocal microscopy. Results: Levels of uDcR2/Cr were significantly higher in IgAN patients and in those with more severe TIF, compared with healthy controls. Serum DcR2 levels were similar across groups. The proportion of IgAN patients with stages 1-2 CKD and T0 was highest among those with uDcR2/Cr 201 ng/g had stages 4-5 CKD and T2. Levels of uDcR2/Cr were positively associated with urinary albumin to creatinine ratio (ACR), urinary N-acetyl-beta-D-glucosaminidase (uNAG)/Cr, and TIF scores and negatively associated with estimated glomerular filtration rate (eGFR). uDcR2/Cr, uNAG, ACR, and eGFR were independent predictors for TIF, with AUC of 0.907 for uDcR2/Cr. This AUC value was higher than that observed for eGFR, uNAG/Cr, or ACR. The sensitivity and specificity of uDcR2/Cr in predicting TIF were 87.0 and 80.5%, respectively. Moreover, uDcR2/Cr levels were positively associated with the percentage of renal DcR2 expression. Renal DcR2 co-localized with alpha-SMA and collagen III in the kidneys of IgAN patients. Conclusions: Levels of uDcR2/Cr were closely associated with the severity of TIF and renal function parameters. uDcR2/Cr represents a potential biomarker for predicting TIF in IgAN patients.