Sun Ci, Shen Lei, Sha Wengang, Zhou Ling, Xu Deyu, Dong Ningzheng
Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Exp Ther Med. 2018 Jan;15(1):487-493. doi: 10.3892/etm.2017.5398. Epub 2017 Oct 30.
Corin is a serine protease that is important for the regulation of blood pressure and water balance. Corin was initially discovered in the heart, however, it has also been detected in kidney cells, though its function in the kidneys is unclear. To further investigate the function of corin in the kidney, the present study analyzed the levels of corin in urine and blood samples collected from normal individuals and patients with primary proteinuric diseases. The associations between the levels of corin, and the cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were then assessed. The results demonstrated that corin was detectable in the urine and plasma following an enzyme-linked immunosorbent assay; the level of corin in the urine was associated with the level of urinary β-microglobulin (P=0.01), which was indicative of renal tubular injury. When compared with normal individuals, the levels of urinary corin in proteinuric patients were markedly increased (P=0.02), and were also associated with IL-1β (P=0.03). This correlation between corin and IL-1β was confirmed using 293 cells. As the IL-1β concentrations increased (0, 0.1, 1, 10 ng/ml), an elevation in the level of corin was observed in the culture medium (P<0.01); however, the amount of corin was not markedly altered in the cell lysate (P>0.05). In addition, when TNF-α reached 10 ng/ml, the level of corin in the medium increased significantly when compared with the control group (0 ng/ml; P=0.02), however, no significant difference in corin levels was detected in the cell lysate. The results suggest that the cytokines IL-1β and TNF-α may increase urinary corin in patients with primary proteinuric kidney diseases. Cytokines may accelerate corin shedding from the cell membrane of renal tubule epithelial cells. These findings indicate that corin may be associated with kidney inflammation and injury.
Corin是一种丝氨酸蛋白酶,对血压调节和水平衡至关重要。Corin最初是在心脏中发现的,然而,在肾细胞中也检测到了它,尽管其在肾脏中的功能尚不清楚。为了进一步研究Corin在肾脏中的功能,本研究分析了从正常个体和原发性蛋白尿疾病患者收集的尿液和血液样本中Corin的水平。然后评估了Corin水平与细胞因子白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)之间的关联。结果表明,通过酶联免疫吸附测定法可在尿液和血浆中检测到Corin;尿液中Corin的水平与尿β-微球蛋白水平相关(P = 0.01),这表明存在肾小管损伤。与正常个体相比,蛋白尿患者尿液中Corin的水平显著升高(P = 0.02),并且也与IL-1β相关(P = 0.03)。使用293细胞证实了Corin与IL-1β之间的这种相关性。随着IL-1β浓度增加(0、0.1、1、10 ng/ml),培养基中Corin水平升高(P < 0.01);然而,细胞裂解物中Corin的量没有明显改变(P > 0.05)。此外,当TNF-α达到10 ng/ml时,与对照组(0 ng/ml;P = 0.02)相比,培养基中Corin的水平显著增加,然而,在细胞裂解物中未检测到Corin水平的显著差异。结果表明,细胞因子IL-1β和TNF-α可能会增加原发性蛋白尿性肾病患者尿液中的Corin。细胞因子可能会加速Corin从肾小管上皮细胞膜上脱落。这些发现表明Corin可能与肾脏炎症和损伤有关。