Tamaki K, Okuda S, Nakayama M, Yanagida T, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Am Soc Nephrol. 1996 Dec;7(12):2578-89. doi: 10.1681/ASN.V7122578.
The expression of transforming growth factor-beta 1 (TGF-beta 1) for hypertensive renal injury was investigated in Dahl salt-sensitive (Dahl-S) rats fed a high-salt (HS; 8% NaCl) diet or a low-salt (LS; 0.3% NaCl) diet for 4 wk. The HS rats developed severe hypertension and renal damage, including glomerulosclerosis and arteriosclerosis. TGF-beta biosynthesis by isolated glomeruli, the TGF-beta localization, and the gene expression of TGF-beta 1, latent TGF-beta binding protein (LTBP), and TGF-beta receptors (Types I, II, and III) were compared between the HS rats and LS rats. A TGF-beta bioassay revealed that the isolated glomeruli from the HS rats secreted a larger amount of latent TGF-beta than those from the LS rats. Northern blotting analysis demonstrated that the HS diet led to the increases in cortical gene expression of TGF-beta 1, LTBP, and TGF-beta receptors, compared with the LS diet. The glomerular biosynthesis of fibronectin and plasminogen activator inhibitor-1 (PAI-1), and cortical mRNA expression for fibronectin, collagen I, and PAI-1 (which may be affected by TGF-beta) in the HS rats were elevated, compared with the LS rats. The latent TGF-beta immunostained by anti-LTBP antibody was localized on the sclerosing glomeruli and vascular walls. Furthermore, fibronectin, collagen I, and PAI-1 were also localized in the sclerotic area. The TGF-beta 1-positive cells, immunostained by antibody for latency-associated peptide of TGF-beta 1, increased in the glomeruli and vascular walls in the HS rats. These results thus suggested that TGF-beta 1 may be related to hypertensive renal injury in this model.
研究了在高盐（HS；8%氯化钠）饮食或低盐（LS；0.3%氯化钠）饮食喂养4周的Dahl盐敏感（Dahl-S）大鼠中，转化生长因子-β1（TGF-β1）在高血压肾损伤中的表达情况。HS大鼠出现了严重的高血压和肾损伤，包括肾小球硬化和动脉硬化。比较了HS大鼠和LS大鼠之间分离肾小球的TGF-β生物合成、TGF-β定位以及TGF-β1、潜伏性TGF-β结合蛋白（LTBP）和TGF-β受体（I型、II型和III型）的基因表达。TGF-β生物测定显示，HS大鼠分离的肾小球比LS大鼠分泌更多的潜伏性TGF-β。Northern印迹分析表明，与LS饮食相比，HS饮食导致皮质中TGF-β1、LTBP和TGF-β受体的基因表达增加。与LS大鼠相比，HS大鼠中纤连蛋白和纤溶酶原激活物抑制剂-1（PAI-1）的肾小球生物合成以及皮质中纤连蛋白、I型胶原和PAI-1（可能受TGF-β影响）的mRNA表达升高。抗LTBP抗体免疫染色的潜伏性TGF-β定位于硬化的肾小球和血管壁。此外，纤连蛋白、I型胶原和PAI-1也定位于硬化区域。用TGF-β1潜伏相关肽抗体免疫染色的TGF-β1阳性细胞在HS大鼠的肾小球和血管壁中增加。因此，这些结果表明TGF-β1可能与该模型中的高血压肾损伤有关。
