Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 10257 Vilnius, Lithuania.
Institute of Biochemistry, Vilnius University Life Sciences Center, 10257 Vilnius, Lithuania.
Medicina (Kaunas). 2023 Sep 27;59(10):1729. doi: 10.3390/medicina59101729.
Congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of the urinary collecting system, known as hydronephrosis or ureterohydronephrosis. The mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin II and TGFβ levels in obstructed ureteral tissue. The aim of the study is to investigate the expression of fibrosis-related genes in obstructive and normal ureteral tissue. It is a monocentric pilot study in which nineteen patients were selected prospectively. 17 patients underwent Hynes-Anderson pyeloplasty due to the PUJO; two patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO); and six patients were chosen for the control group: five underwent nephrectomies due to the kidney tumor and one underwent upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR was performed to evaluate the relative expression of Tgfb1, Mmp1, Timp1, Pai1, Ctgf, and Vegfa. Expression levels of the Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and a Wilcoxon rank-sum test was performed to determine the statistical significance of the differences. Significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, and Pai1 was found. These findings suggest that tissue fibrosis, similar to other tissues and organs, is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF expression is indicative of the developmental origin of obstruction.
先天性输尿管狭窄是导致尿路引流障碍和随后的尿收集系统扩张（即肾积水或输尿管积水）的主要原因之一。导致梗阻的机制尚不清楚。在大鼠模型中的多项研究表明，梗阻性输尿管组织中的血管紧张素 II 和 TGFβ 水平升高。本研究旨在研究纤维化相关基因在梗阻性和正常输尿管组织中的表达。这是一项单中心的前瞻性研究，共选择了 19 名患者。17 名患者因肾盂输尿管交界处梗阻（PUJO）行 Hynes-Anderson 肾盂成形术；2 名患者因输尿管膀胱交界处梗阻（UVJO）行输尿管膀胱再吻合术；6 名患者为对照组：5 名因肾肿瘤行肾切除术，1 名因双肾盂伴肾盂输尿管连接部正常行上极半肾切除术。组织 RNA 在液氮中冷冻活检样本后化学提取，核酸分离后立即进行 cDNA 合成。qPCR 用于评估 Tgfb1、Mmp1、Timp1、Pai1、Ctgf 和 Vegfa 的相对表达。使用 Gapdh 和 Gpi 基因（几何平均值）的表达水平来计算研究基因的相对表达。在计算实验组置信区间之前，先剔除离群值，然后进行 Wilcoxon 秩和检验以确定差异的统计学意义。在 Ctgf 基因表达水平上观察到健康和狭窄组织样本之间存在显著差异，患病组织样本的表达水平较低。在 Tgfb1、Timp1、Vegfa、Mmp1 和 Pai1 的表达水平上未发现统计学差异。这些发现表明，组织纤维化（与其他组织和器官相似）不是狭窄的主要原因，至少在手术时不是。CTGF 表达降低表明梗阻的发育起源。
