Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, The Renal Research Institution of Zhengzhou University, Zhengzhou, China.
Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, The Renal Research Institution of Zhengzhou University, Zhengzhou, China,
Kidney Blood Press Res. 2021;46(1):31-40. doi: 10.1159/000508079. Epub 2020 Dec 18.
BACKGROUND/AIMS: Renal vascular injury accounts for the poor outcomes of patients with IgA nephropathy (IgAN). In this study, we investigated whether endostatin, a potent inhibitor of angiogenesis, is associated with IgAN.
Serum endostatin levels were detected in patients with IgAN, disease controls, and healthy controls, and the correlation among endostatin and clinicopathologic manifestations, as well as prognosis in patients with IgAN, was analyzed. In addition, serum endostatin levels were compared in patients "before" and "after" treatment. Data on endostatin expression in the renal interstitium of patients with IgAN were downloaded and analyzed from the GSE35489 array in the GEO database. The poly-IgA1 (pIgA) immune complex is widely recognized as the "trigger" of IgAN initiation. pIgA in the plasma of patients was extracted and used to stimulate human glomerular endothelial cells (GECs). Endostatin, IL-6, and CXCL1 in the cell supernatant were detected by ELISA kits.
We found that serum endostatin levels were significantly increased in patients with IgAN, as was endostatin expression in the renal interstitium. Patients with IgAN were divided into 2 groups according to the median value. The high endostatin expression group had significantly higher levels of serum creatinine and BUN and more severe tubular/interstitial damage. Moreover, patients with arteriolar injury and endothelial cell proliferation had higher serum endostatin levels. Patients with high serum endostatin levels had poor prognosis. According to the in vitro experiment, the GEC apoptosis rate and the supernatant levels of endostatin, IL-6, and CXCL1 were significantly increased following pIgA stimulation.
Our study found that elevated endostatin expression was associated with disease severity and poor prognosis in patients with IgAN and can be upregulated by pIgA, but how it participates in the pathogenesis of IgAN deserves further exploration.
背景/目的：IgA 肾病（IgAN）患者的不良预后与肾血管损伤有关。本研究旨在探讨血管内皮抑制素（一种有效的血管生成抑制剂）是否与 IgAN 相关。
检测 IgAN 患者、疾病对照者和健康对照者的血清血管内皮抑制素水平，分析血管内皮抑制素与 IgAN 患者临床病理表现及预后的相关性。此外，比较了 IgAN 患者治疗前后的血清血管内皮抑制素水平。从 GEO 数据库的 GSE35489 数组中下载并分析了 IgAN 患者肾间质中血管内皮抑制素表达的数据。多聚 IgA1（pIgA）免疫复合物被广泛认为是 IgAN 发病的“触发因素”。从患者血浆中提取 pIgA 并用其刺激人肾小球内皮细胞（GEC）。通过 ELISA 试剂盒检测细胞上清液中的血管内皮抑制素、IL-6 和 CXCL1。
我们发现，IgAN 患者血清血管内皮抑制素水平显著升高，肾间质血管内皮抑制素表达也升高。根据中位数将 IgAN 患者分为两组。高血管内皮抑制素表达组的血清肌酐和 BUN 水平显著升高，肾小管/间质损伤更严重。此外，有小动脉损伤和内皮细胞增殖的患者血清血管内皮抑制素水平更高。高血清血管内皮抑制素水平的患者预后不良。根据体外实验，pIgA 刺激后 GEC 凋亡率以及上清液中血管内皮抑制素、IL-6 和 CXCL1 的水平均显著升高。
本研究发现，升高的血管内皮抑制素表达与 IgAN 患者的疾病严重程度和预后不良相关，可被 pIgA 上调，但它如何参与 IgAN 的发病机制值得进一步探讨。
