骨粘连蛋白：一种新型的组织和尿液生物标志物，可诱导肾小管细胞产生协调的间充质表型，导致进行性肾损伤。
Periostin: novel tissue and urinary biomarker of progressive renal injury induces a coordinated mesenchymal phenotype in tubular cells.
机构信息
Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, USA.
出版信息
Nephrol Dial Transplant. 2012 Jul;27(7):2702-11. doi: 10.1093/ndt/gfr670. Epub 2011 Dec 13.
BACKGROUND
Periostin acts as an adhesion molecule during bone formation. Knowledge of its expression in kidney injury is scant.
METHODS
We investigated periostin function and expression in vivo in Sprague-Dawley rats after 5/6 nephrectomy (Nx), in DBA2J mice with streptozotocin-induced diabetic nephropathy (SZ-DN) and unilateral ureteral obstruction (UUO) and in vitro in mouse distal collecting tubular cells (MDCT) and in tissue and urine from chronic kidney disease (CKD) patients.
RESULTS
Periostin messenger RNA was increased after 5/6Nx and SZ-DN demonstrating generalizability of the increment in renal injury. Periostin was expressed predominantly in distal tubule (DT) epithelial cell cytoplasm in situ, in cells shed into the lumen, and, in lesser abundance, in glomeruli undergoing obsolescence, arterioles and in the tubulointerstitium in extracellular and intracellular locations. In affected DT after 5/6Nx, periostin expression appeared de novo, E-cadherin became undetectable and tubule cells displayed the mesenchymal marker proteins fibroblast-specific protein-1 (FSP1) and matrix metalloproteinase-9 (MMP9). Periostin overexpression in cultured MDCT cells dramatically induced MMP9 and FSP1 protein and suppressed E-cadherin. Periostin short interfering RNA blocked these changes. Urine periostin excretion increased over time after 5/6Nx, and it was also excreted in the urine of CKD patients. Urine periostin enzyme-linked immunosorbent assay at a cutoff of 32.66 pg/mg creatinine demonstrated sensitivity and specificity for distinguishing patients with CKD from healthy people (92.3 and 95.0%, respectively) comparing favorably with urine neutrophil gelatinase-associated lipocalin.
CONCLUSION
These data demonstrate that periostin is a mediator and marker of tubular dedifferentiation and a promising tissue and urine biomarker for kidney injury in experimental models and in clinical renal disease.
背景
层粘连蛋白在骨形成过程中作为黏附分子发挥作用。其在肾损伤中的表达知之甚少。
方法
我们在 Sprague-Dawley 大鼠 5/6 肾切除（Nx）、链脲佐菌素诱导的糖尿病肾病（SZ-DN）和单侧输尿管梗阻（UUO）的 DBA2J 小鼠以及体外鼠远曲收集管细胞（MDCT）和慢性肾脏病（CKD）患者的组织和尿液中，研究了层粘连蛋白的功能和表达。
结果
5/6Nx 和 SZ-DN 后，层粘连蛋白信使 RNA 增加，表明肾损伤的增加具有普遍性。层粘连蛋白主要在远曲小管（DT）上皮细胞的细胞质中表达，在脱落到管腔中的细胞中表达，在数量较少的情况下，在进行衰老的肾小球、小动脉和细胞外和细胞内位置的小管间质中表达。在 5/6Nx 后的受影响的 DT 中，层粘连蛋白表达似乎是新出现的，E-钙黏蛋白变得无法检测，肾小管细胞显示间充质标记蛋白纤维连接蛋白特异性蛋白-1（FSP1）和基质金属蛋白酶-9（MMP9）。在培养的 MDCT 细胞中过表达层粘连蛋白，显著诱导 MMP9 和 FSP1 蛋白，并抑制 E-钙黏蛋白。层粘连蛋白短发夹 RNA 阻断了这些变化。5/6Nx 后，尿液中层粘连蛋白的排泄随时间增加，在 CKD 患者的尿液中也排泄。尿液中层粘连蛋白酶联免疫吸附试验的截断值为 32.66 pg/mg 肌酐，用于区分 CKD 患者和健康人群，其灵敏度和特异性分别为 92.3%和 95.0%，优于尿液中性粒细胞明胶酶相关脂质运载蛋白。
结论
这些数据表明，层粘连蛋白是肾小管去分化的介质和标志物，是实验模型和临床肾脏疾病中肾损伤的有前途的组织和尿液生物标志物。
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