Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-beta 1 and glucocorticoids.
Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-beta 1 and glucocorticoids.
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通过转化生长因子-β1 和糖皮质激素对人肺成纤维细胞和白血病细胞中肝细胞生长因子基因表达的负调节。
DOI：
10.1016/s0021-9258(19)73982-9
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Toshikazu Nakamura
中科院分区：
文献类型：
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作者：
Kunio Matsumoto;H. Tajima;H. Okazaki;Toshikazu Nakamura
肝细胞生长因子（HGF）是一种间充质衍生因子，可调节上皮细胞和内皮细胞的生长、运动和形态发生，作为肝和肾再生的肝营养因子和肾营养因子。我们现在已经获得的证据表明，转化生长因子- β 1 （tgf - β 1）和糖皮质激素是HGF基因表达的负调控因子。在MRC-5人胚胎肺成纤维细胞和HL-60人早幼粒细胞白血病细胞培养物中加入tgf - β 1或地塞米松后，10 ng/ml tgf - β 1和10(-6)M地塞米松分别抑制培养液中HGF的分泌量为对照组的30-40%和40-50%。tgf - β 1和地塞米松对MRC-5细胞HGF合成的抑制作用是叠加的，提示tgf - β 1和地塞米松的作用机制不同。氢化可的松对HGF的抑制作用与地塞米松相同；然而，睾酮、雌三醇和-雌二醇没有影响。通过[35S]蛋氨酸脉冲标记和随后的免疫沉淀测量，MRC-5细胞中HGF的合成率被10 ng/ml tgf - β 1抑制到对照组的30-40%，被10(-6)M地塞米松抑制到30-45%。tgf - β 1和地塞米松剂量依赖性地抑制MRC-5细胞和HL-60细胞中HGF mRNA水平；10 ng/ml tgf - β 1抑制MRC-5细胞和HL-60细胞HGF mRNA水平分别为对照培养的32%和35%，10(-6)M地塞米松抑制HGF mRNA水平分别为43%和38%。因此，tgf - β 1和糖皮质激素似乎通过抑制HGF基因的表达来抑制HGF的合成。我们认为tgf - β 1或糖皮质激素对HGF基因表达的负调控可能参与了组织再生过程中的生理或病理过程。
Hepatocyte growth factor (HGF), a mesenchymal-derived factor which regulates growth, motility, and morphogenesis of epithelial and endothelial cells, functions as a hepatotrophic and renotrophic factor for regeneration of the liver and kidney. We have now obtained evidence that transforming growth factor-beta 1 (TGF-beta 1) and glucocorticoids are negative regulators for HGF gene expression. When TGF-beta 1 or dexamethasone was added to cultures of MRC-5 human embryonic lung fibroblasts and HL-60 human promyelocytic leukemic cells, the amount of HGF secreted into the culture medium was inhibited to 30-40% of that of control cultures by 10 ng/ml TGF-beta 1 and to 40-50% by 10(-6) M dexamethasone. The inhibitory effect of TGF-beta 1 and dexamethasone on HGF synthesis in MRC-5 cells was additive, thereby suggesting that TGF-beta 1 and dexamethasone exert effects through distinct mechanisms. Hydrocortisone also inhibited HGF synthesis with the same potency as dexamethasone; however, testosterone, estriol, and beta-estradiol had no effect. The rate of HGF synthesis in MRC-5 cells, as measured by pulse labeling with [35S]methionine and subsequent immunoprecipitation, was suppressed to 30-40% of the control with 10 ng/ml TGF-beta 1, and to 30-45% by 10(-6) M dexamethasone. HGF mRNA levels in MRC-5 cells and HL-60 cells were dose-dependently suppressed by TGF-beta 1 and dexamethasone; 10 ng/ml TGF-beta 1 suppressed HGF mRNA levels to 32% and 35% of control culture, respectively, in MRC-5 cells and HL-60 cells, and 10(-6) M dexamethasone suppressed to 43% and 38%, respectively. Thus, TGF-beta 1 and glucocorticoids seem to inhibit HGF synthesis by suppressing the expression of the HGF gene. We propose that a negative regulation of HGF gene expression by TGF-beta 1 or glucocorticoids may be involved in physiological or pathological processes during tissue regeneration.