Matsumoto K, Tajima H, Okazaki H, Nakamura T
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
J Biol Chem. 1992 Dec 15;267(35):24917-20.
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.
肝细胞生长因子（HGF）是一种间充质来源的因子，可调节上皮细胞和内皮细胞的生长、运动及形态发生，作为肝营养因子和肾营养因子参与肝脏和肾脏的再生。我们现已获得证据表明，转化生长因子-β1（TGF-β1）和糖皮质激素是HGF基因表达的负调节因子。当将TGF-β1或地塞米松添加到MRC-5人胚肺成纤维细胞和HL-60人早幼粒细胞白血病细胞的培养物中时，分泌到培养基中的HGF量被10 ng/ml TGF-β1抑制至对照培养物的30%-40%，被10⁻⁶ M地塞米松抑制至40%-50%。TGF-β1和地塞米松对MRC-5细胞中HGF合成的抑制作用具有相加性，这表明TGF-β1和地塞米松通过不同机制发挥作用。氢化可的松也以与地塞米松相同的效力抑制HGF合成；然而，睾酮、雌三醇和β-雌二醇则无作用。通过用[³⁵S]甲硫氨酸脉冲标记并随后进行免疫沉淀测定，MRC-5细胞中HGF的合成速率被10 ng/ml TGF-β1抑制至对照的30%-40%，被10⁻⁶ M地塞米松抑制至30%-45%。MRC-5细胞和HL-60细胞中的HGF mRNA水平被TGF-β1和地塞米松剂量依赖性地抑制；10 ng/ml TGF-β1分别将MRC-5细胞和HL-60细胞中的HGF mRNA水平抑制至对照培养物的32%和35%，10⁻⁶ M地塞米松分别抑制至43%和38%。因此，TGF-β1和糖皮质激素似乎通过抑制HGF基因的表达来抑制HGF合成。我们提出，TGF-β1或糖皮质激素对HGF基因表达的负调节可能参与组织再生过程中的生理或病理过程。
