Renal Division, Department of Internal Medicine, Gent University Hospital, Gent, Belgium.
Nephrol Dial Transplant. 2010 May;25(5):1688-96. doi: 10.1093/ndt/gfq036. Epub 2010 Feb 11.
Dietary salt intake has been linked to hypertension and cardiovascular disease through volume-mediated effects. Accumulating evidence points to direct negative influence of salt intake independent of volume overload, such as cardiac and renal fibrosis, mediated through transforming growth factor beta (TGF-beta). Epithelial-to-mesenchymal transition (EMT) has been implicated as a key process in chronic fibrotic diseases, such as chronic kidney disease or heart failure. The potential role of dietary salt intake on cell transdifferentiation has never been investigated. This study analysed the effect of dietary salt intake on EMT and fibrosis in the peritoneal membrane (PM) in a rat model.
Twenty-eight Wistar rats were randomized to a normal salt (NS) or a high salt (HS) intake. NS and HS rats had free access to tap water or NaCl 2% as drinking water, respectively. After 2 weeks, samples of peritoneum were taken, and TGF-beta(1), Interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) mRNA expression were quantified with qRT-PCR. Fibrosis and submesothelial PM thickness were scored. EMT was evaluated using fluorescence staining with cytokeratin and alpha smooth muscle actin (alpha-SMA).
Dietary salt intake caused peritoneal fibrosis and thickening of the submesothelial layer and induced EMT as identified by colocalization of cytokeratin and alpha-SMA in cells present in the submesothelial layer. Peritoneal TGF-beta(1) and IL-6 mRNA expression were upregulated in the HS group.
High dietary salt intake induces EMT and peritoneal fibrosis, a process coinciding with upregulation of TGF-beta1.
饮食盐摄入量与高血压和心血管疾病通过容量介导的作用有关。越来越多的证据表明，盐摄入量对心脏和肾脏纤维化等体积超负荷以外的直接负面影响，是通过转化生长因子β（TGF-β）介导的。上皮间质转化（EMT）已被认为是慢性纤维化疾病（如慢性肾脏病或心力衰竭）的关键过程。饮食盐摄入量对细胞转化的潜在作用尚未被研究过。本研究分析了饮食盐摄入量对大鼠模型腹膜（PM）中 EMT 和纤维化的影响。
28 只 Wistar 大鼠随机分为正常盐（NS）或高盐（HS）摄入组。NS 和 HS 大鼠可自由饮用自来水或 2%NaCl 水。2 周后，取腹膜样本，用 qRT-PCR 定量 TGF-β（1）、白细胞介素 6（IL-6）和血管内皮生长因子（VEGF）mRNA 的表达。纤维化和亚基膜 PM 厚度进行评分。使用细胞角蛋白和α平滑肌肌动蛋白（α-SMA）的荧光染色评估 EMT。
饮食盐摄入导致腹膜纤维化和亚基膜层增厚，并诱导 EMT，通过存在于亚基膜层中的细胞中细胞角蛋白和α-SMA 的共定位来识别。HS 组中腹膜 TGF-β（1）和 IL-6 mRNA 的表达上调。
高饮食盐摄入诱导 EMT 和腹膜纤维化，这一过程与 TGF-β1 的上调相一致。
