Ohyama K, Seyer J M, Raghow R, Kang A H
Department of Medicine, University of Tennessee, Memphis.
Biochim Biophys Acta. 1990 Jul 12;1053(2-3):173-8. doi: 10.1016/0167-4889(90)90010-b.
Rats were administered CCl4, a well-defined nephrotoxin, for 20 weeks to produce glomerular sclerosis. Tubular degeneration and necrosis with interstitial fibrosis was clearly evident by histological examination. Kidneys were homogenized in phosphate-buffered saline and a collagen synthesis-stimulating factor was isolated by Sephadex G-50 gel filtration. The 5 kDa component stimulated both type I and type IV procollagen synthesis by mesangial cells and type I procollagen synthesis by rat skin fibroblasts. In each cell type, 2-6-fold increases in procollagen protein production or cell proliferation was noted. The steady-state levels of mRNA encoding for procollagen alpha 1(I) and procollagen alpha 1(IV) chains in mesangial cells were determined by by hybridization to their corresponding cDNA clones. The type I procollagen mRNA was elevated 1.4-fold compared to a 1.6-fold increase in mRNA encoding for type IV procollagen. The similar properties and chemical characteristics of this fibrogenic factor with a factor from fibrotic liver suggests they are the same and that a common endogenous collagen synthesis stimulator may be present in fibrosing organs, thus providing a driving force for collagen over-production.
给大鼠施用四氯化碳（一种明确的肾毒素）20周以诱导肾小球硬化。组织学检查清楚地显示出肾小管变性、坏死伴有间质纤维化。将肾脏在磷酸盐缓冲盐水中匀浆，并通过葡聚糖凝胶G - 50凝胶过滤分离出一种胶原合成刺激因子。该5 kDa成分刺激系膜细胞的I型和IV型前胶原合成以及大鼠皮肤成纤维细胞的I型前胶原合成。在每种细胞类型中，均观察到前胶原蛋白产生或细胞增殖增加了2 - 6倍。通过与相应的cDNA克隆杂交来测定系膜细胞中编码前胶原α1(I)链和前胶原α1(IV)链的mRNA的稳态水平。与编码IV型前胶原的mRNA增加1.6倍相比，I型前胶原mRNA升高了1.4倍。这种致纤维化因子与来自纤维化肝脏的一种因子具有相似的性质和化学特征，这表明它们是相同的，并且在纤维化器官中可能存在一种共同的内源性胶原合成刺激物，从而为胶原过度产生提供了驱动力。
