HEPATOCYTE PROLIFERATION AND GENE-EXPRESSION INDUCED BY TRIIODOTHYRONINE IN-VIVO AND IN-VITRO
HEPATOCYTE PROLIFERATION AND GENE-EXPRESSION INDUCED BY TRIIODOTHYRONINE IN-VIVO AND IN-VITRO
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DOI：
10.1002/hep.1840200521
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发表时间：
1994-11-01
期刊：
影响因子：
13.5
通讯作者：
STARZL, TE
中科院分区：
文献类型：
--
作者：
FRANCAVILLA, A;CARR, BI;STARZL, TE
皮下注射激素三碘甲状腺原氨酸在大鼠中导致在24小时的峰值血液水平与返回到基线由96 hr. The注射刺激肝再生反应，类似的时间和DNA合成的幅度（峰值，24小时），诱导40%的肝切除。主要增殖为肝细胞。尽管已知部分肝切除术后转化生长因子-α、转化生长因子-β和c-Ha-ras的基因表达存在一些时间差异，但这些变化的总体特征与部分切除术后相似。该效应具有肝脏特异性，可重复三次，且在同一只动物中以10天间隔注射，反应无减弱。在肾脏或肠道中未检测到反应。在完整动物中的这种作用与三碘甲状腺原氨酸刺激培养物中肝细胞的最小能力形成对比。然而，当培养基中富含表皮生长因子时，对三碘甲腺原氨酸有剂量相关反应。这些实验的整体提供了一个初步的基础，在体内增生性肝脏的条件允许新基因的转染，作为替代部分肝切除术的药理学技术的创建。虽然三碘甲状腺原氨酸是使用的试验药物，但其他肝生长因子单独或联合使用也可用于此目的。
Subcutaneous injections of hormone triiodothyronine in rats resulted in peak blood levels at 24 hr with return to baseline by 96 hr. The injections stimulated a liver regeneration response that resembled in timing and in magnitude of DNA synthesis (peak, 24 hr) that induced by 40% hepatic resection. The principal proliferation was of hepatocytes. Although there were some temporal differences from the gene expression of transforming growth factor-alpha, transforming growth factor-beta, and c-Ha-ras that are known to follow partial hepatectomy, the overall profile of these changes was similar to those after partial resection. The effect was liver specific and could be reproduced three times with no diminution in response in the same animal with injections at 10-day intervals. No response was detected in kidney or intestine. This effect in intact animals contrasted with the minimal ability of triiodothyronine to stimulate hepatocytes in culture. However, when the culture medium was enriched with epidermal growth factor, there was a dose-related response to triiodothyronine. The totality of these experiments provides a preliminary basis for the creation with pharmacological techniques of an in vivo hyperplastic hepatic condition permissive of transfection of new genes, as an alternative to partial hepatectomy. Although triiodothyronine was the test agent used, other hepatic growth factors singly or in combination could be candidates for this purpose.