Graduate Program in Biomedical Sciences, University Center of the Hermínio Ometto Foundation, Araras, São Paulo 13607-339, Brazil.
Mol Med Rep. 2019 Nov;20(5):4467-4476. doi: 10.3892/mmr.2019.10722. Epub 2019 Oct 2.
Epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition are processes that can occur under different biological conditions, including tissue healing due to hypertension and oxidative stress. The purpose of the present study was to evaluate the differences in gene expression of epithelial/endothelial and mesenchymal markers in different tissues. A two-kidney, one-clip (2K1C) renovascular hypertension rat model was used. Hypertension was induced by the clipping of the left renal artery; the rats were randomized into sham and 2K1C groups and monitored for up to 4 weeks. The gene expressions of E-cadherin (E-cad), N-cadherin (N-cad), α-smooth muscle actin (α-SMA), collagen I (COL1A1), collagen III (COL3A1) and hepatocyte growth factor (HGF) were determined by reverse transcription-PCR. The levels of the cytokines transforming growth factor-β1, tumor necrosis factor-α, interleukin (IL)-4, IL-6 and IL-10 were evaluated using ELISAs. The levels of thiobarbituric acid reactive substances and thiol groups were measured to evaluate oxidative stress. All analyses were performed on the liver, heart and kidneys tissues of sham and model rats. The 2K1C animals exhibited a higher systolic blood pressure, as well as cardiac hypertrophy and atrophy of the left kidney. Fibrotic alterations in the heart and kidneys were observed, as was an increase in the collagen fiber areas, and higher levels of inflammatory cytokines, which are associated with the increased expression of fibroproliferative and anti-fibrotic genes. Renovascular hypertension regulated epithelial/endothelial and mesenchymal markers, including E-cad, N-cad, α-SMA and COL1A1 in the kidneys and heart. EMT in the kidneys was mediated by an increased level of inflammatory and profibrotic cytokines, as well as by oxidative stress. The data in the present study suggested that the expression of epithelial/endothelial and mesenchymal markers are differentially regulated by hypertension in the liver, heart and kidneys.
上皮-间充质转化（EMT）和内皮-间充质转化是在不同的生物学条件下发生的过程，包括高血压和氧化应激引起的组织修复。本研究的目的是评估不同组织中上皮/内皮和间充质标志物的基因表达差异。使用双肾一夹（2K1C）肾血管性高血压大鼠模型。通过夹闭左肾动脉诱导高血压；将大鼠随机分为假手术和 2K1C 组，并监测长达 4 周。通过逆转录-PCR 测定 E-钙黏蛋白（E-cad）、N-钙黏蛋白（N-cad）、α-平滑肌肌动蛋白（α-SMA）、I 型胶原（COL1A1）、III 型胶原（COL3A1）和肝细胞生长因子（HGF）的基因表达。使用 ELISA 测定转化生长因子-β1、肿瘤坏死因子-α、白细胞介素（IL）-4、IL-6 和 IL-10 的细胞因子水平。通过测定硫代巴比妥酸反应物质和巯基来评估氧化应激。对 sham 和模型大鼠的肝、心和肾组织进行所有分析。2K1C 动物表现出更高的收缩压，以及心脏肥大和左肾萎缩。观察到心脏和肾脏的纤维化改变，胶原纤维面积增加，炎症细胞因子水平升高，这与成纤维增殖和抗纤维化基因的表达增加有关。肾血管性高血压调节了肾脏和心脏中的上皮/内皮和间充质标志物，包括 E-cad、N-cad、α-SMA 和 COL1A1。肾脏的 EMT 是由炎症和促纤维化细胞因子水平升高以及氧化应激介导的。本研究的数据表明，肝脏、心脏和肾脏中的高血压对上皮/内皮和间充质标志物的表达有不同的调节作用。
