TRANSFORMING GROWTH FACTOR-BETA MESSENGER-RNA INCREASES DURING LIVER-REGENERATION - A POSSIBLE PARACRINE MECHANISM OF GROWTH-REGULATION

TRANSFORMING GROWTH FACTOR-BETA MESSENGER-RNA INCREASES DURING LIVER-REGENERATION - A POSSIBLE PARACRINE MECHANISM OF GROWTH-REGULATION
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DOI:
10.1073/pnas.85.5.1539
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发表时间:
1988-03-01
影响因子:
11.1
通讯作者:
FAUSTO, N
FAUSTO, N
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BRAUN, L;MEAD, JE;FAUSTO, N

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转化生长因子β(TGF-β)是一种具有多种生物学特性的生长因子,包括刺激和抑制细胞增殖。为了确定TGF-β.参与体内肝细胞生长反应,我们测量了TGF-β的水平。大鼠正常肝脏和部分肝切除后肝再生过程中mRNA的表达。TGF-.beta. mRNA在再生肝脏中增加,并在ras原癌基因表达达到峰值后达到峰值(约为基础水平的8倍)。尽管来自正常和再生肝的肝细胞对TGF-β有应答,它们不合成TGF-β。mRNA。相反,该信息存在于肝脏非实质细胞中,并且在富含内皮细胞的细胞组分中特别丰富。TGF-.beta.抑制正常和再生肝的肝细胞中表皮生长因子诱导的体外DNA合成,尽管剂量-反应曲线根据所用培养基而变化。我们得出结论,TGF-β.可能作为抑制性旁分泌环的效应物,其在肝再生期间被激活,可能防止不受控制的肝细胞增殖。
Transforming growth factor .beta. (TGF-.beta.) is a growth factor with multiple biological properties including stimulation and inhibition of cell proliferation. To determine whether TGF-.beta. is involved in hepatocyte growth responses in vivo, we measured the levels of TGF-.beta. mRNA in normal liver and during liver regeneration after partial hepatectomy in rats. TGF-.beta. mRNA increases in the regenerating liver and reaches a peak (about 8 times higher than basal levels) after taken place and after the peak expression of the ras protooncogenes. Although hepatocytes from normal and regenerating liver respond to TGF-.beta., they do not synthesize TGF-.beta. mRNA. Instead, the message is present in liver nonparenchymal cells and is particularly abundant in cell fractions enriched for endothelial cells. TGF-.beta. inhibits epidermal growth factor-induced DNA synthesis in vitro in hepatocytes from normal and regenerating liver, although the dose-response curves vary according to the culture medium used. We conclude that TGF-.beta. may function as the effector of an inhibitory paracrine loop that is activated during liver regeneration, perhaps to prevent uncontrolled hepatocyte proliferation.