Tamaki K, Okuda S, Ando T, Iwamoto T, Nakayama M, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kidney Int. 1994 Feb;45(2):525-36. doi: 10.1038/ki.1994.68.
The role of transforming growth factor-beta 1 (TGF-beta 1) for renal injury was investigated in the chronic model of progressive renal disease in rats induced by the injection of adriamycin. The renal cortical tissues were sampled at weeks 4, 8 and 16 for histological examination, either cortical or glomerular cell culture, and RNA extraction. A progressive increase in fibronectin synthesis was found in metabolically labeled cortical or glomerular culture at week 8 or 16, correlating with the degree of glomerulosclerosis and interstitial fibrosis. TGF-beta bioassay (mink lung epithelial cell assay) showed a progressive increase in latent TGF-beta secretion from cortex and glomeruli, while the amount of active TGF-beta was small. The peak of latent TGF-beta levels at week 16 coincided with the intense TGF-beta 1 staining of inflammatory cells dispersed in the interstitium and glomeruli. Northern blotting demonstrated the difference in the mRNA expression patterns of TGF-beta 1 and latent TGF-beta 1 binding protein (LTBP) in the cortex. TGF-beta 1 mRNA was constantly high throughout the experiment, while LTBP mRNA increased progressively and reached a peak at week 16. Furthermore, mRNA levels of fibronectin, procollagen alpha 2(I), and TGF-beta type II and type III receptors increased progressively in a similar pattern to the renal histological changes. These temporal and spacial relationships between the renal histological changes and the increased expression of TGF-beta 1 and TGF-beta receptors may thus suggest that TGF-beta 1 plays an important role in the process of the renal fibrosis and sclerosis.
通过注射阿霉素诱导大鼠建立慢性进行性肾病模型，研究转化生长因子-β1（TGF-β1）在肾损伤中的作用。在第4、8和16周采集肾皮质组织，用于组织学检查、皮质或肾小球细胞培养以及RNA提取。在第8周或16周的代谢标记皮质或肾小球培养物中发现纤连蛋白合成逐渐增加，这与肾小球硬化和间质纤维化程度相关。TGF-β生物测定（貂肺上皮细胞测定）显示皮质和肾小球中潜伏性TGF-β分泌逐渐增加，而活性TGF-β的量较少。第16周潜伏性TGF-β水平的峰值与分散在间质和肾小球中的炎症细胞强烈的TGF-β1染色一致。Northern印迹法显示皮质中TGF-β1和潜伏性TGF-β1结合蛋白（LTBP）的mRNA表达模式存在差异。在整个实验过程中，TGF-β1 mRNA一直处于高水平，而LTBP mRNA逐渐增加并在第16周达到峰值。此外，纤连蛋白、前胶原α2（I）以及TGF-β II型和III型受体的mRNA水平以与肾脏组织学变化相似的模式逐渐增加。因此，肾脏组织学变化与TGF-β1和TGF-β受体表达增加之间的这些时间和空间关系可能表明TGF-β1在肾纤维化和硬化过程中起重要作用。
