EXCESS IRON INTO HEPATOCYTES IS REQUIRED FOR ACTIVATION OF COLLAGEN TYPE-I GENE DURING EXPERIMENTAL SIDEROSIS
EXCESS IRON INTO HEPATOCYTES IS REQUIRED FOR ACTIVATION OF COLLAGEN TYPE-I GENE DURING EXPERIMENTAL SIDEROSIS
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DOI：
10.1016/0016-5085(94)90237-2
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发表时间：
1994-10-01
期刊：
影响因子：
29.4
通讯作者：
PIETRANGELO, A
中科院分区：
文献类型：
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作者：
GUALDI, R;CASALGRANDI, G;PIETRANGELO, A
背景/目的：肝纤维化和肝硬化是铁超载患者常见的病理表现。本研究旨在评估铁在体内靶向肝实质细胞和非实质细胞是否会对胶原基因活性产生不同的影响。方法：用铁饲料或右旋糖酐铁肌肉注射大鼠，对肝脏标本进行原位杂交分析。结果：这些铁处理分别决定了实质或网状内皮细胞铁超载。铁在不同肝细胞中的典型分布通过组织化学记录，并通过铁蛋白L互补RNA探针原位杂交分析证实。在铁喂养大鼠中，原位杂交分析在I区和ii区发现了胶原I型信使RNA进入非实质细胞的信号。在非实质细胞铁超载的大鼠中，在铁负载的非实质细胞内或附近未检测到胶原基因表达的激活。定量Northern blot分析也证实了这些发现。结论：本研究结果表明，无论总肝铁负荷如何，铁选择性定位到肝细胞（即实质细胞）是啮齿动物长期铁过载时激活胶原基因所必需的。
Background/Aims: Liver fibrosis and cirrhosis represent common pathological findings in humans with iron overload. This study was undertaken to assess whether in vivo targeting of iron to liver parenchymal or nonparenchymal cells would differently affect collagen gene activity. Methods: Rats were treated with an iron diet or intramuscular injections of iron dextran, and in situ hybridization analyses on liver samples were performed. Results: These iron treatments determined parenchymal or reticuloendothelial cell iron overload, respectively. The typical distribution of iron into different liver cells was documented by histochemistry and confirmed by in situ hybridization analysis with a ferritin L complementary RNA probe. In iron-fed rats, in situ hybridization analysis identified a signal for collagen type I messenger RNA into nonparenchymal cells in zones I and ii. In rats with nonparenchymal cell iron overload, no activation of collagen gene expression was detected into or near iron-laden nonparenchymal cells. These findings were also confirmed by quantitative Northern blot analysis. Conclusions: The results of this study indicate that, regardless of the total hepatic iron burden, selective localization of iron into liver cells (i.e., parenchymal cells) is required for the activation of collagen gene during long-term iron overload in rodents.