Russell W E, Coffey R J, Ouellette A J, Moses H L
Endocrine-Metabolic Unit of the Children's Service, Massachusetts General Hospital, Boston.
Proc Natl Acad Sci U S A. 1988 Jul;85(14):5126-30. doi: 10.1073/pnas.85.14.5126.
Type beta transforming growth factor (TGF-beta), a factor produced by many cell types, is a potent inhibitor of hepatocyte DNA synthesis in vitro. To determine whether TGF-beta can influence hepatocyte proliferation in vivo, its effects were examined on the regenerative response of liver to partial hepatectomy (PH) in the rat. Porcine platelet-derived TGF-beta 1 (0.5 micrograms), administered intravenously at the time of PH and 11 hr later, reduced the fraction of hepatocytes engaged in DNA synthesis 22 hr after PH by 67% and inhibited the rate of hepatic [3H]thymidine incorporation by 50%. TGF-beta 2 produced a similar effect. A single dose of 0.5 micrograms of TGF-beta 1 given 11 hr after PH reduced liver [3H]thymidine incorporation by 32%; 4.5 micrograms of TGF-beta 1 or TGF-beta 2 inhibited DNA synthesis by 88% and the labeling index by 86%. Although sensitive to TGF-beta administered 11 hr after PH, late in the G1 phase of the cell cycle, a single dose of 0.5 micrograms given at the time of PH did not significantly influence DNA synthesis 22 hr after PH. The inhibitory effects of TGF-beta were transient; rats treated with two 0.5-microgram doses of TGF-beta at 0 and 11 hr had completely restored their original liver DNA mass 8 days after PH. Administration of 0.5 microgram of either TGF-beta 1 or TGF-beta 2 every 12 hr for 5 days failed to suppress the recovery of hepatic DNA mass. However, the nuclear labeling index of the TGF-beta-treated animals was significantly higher than that of the controls. There was no evidence of cytotoxicity from TGF-beta, as determined by liver histology and plasma concentrations of glucose, insulin-like growth factor I, and two hepatic enzymes. Thus, TGF-beta 1 and TGF-beta 2 reversibly inhibit the proliferative response of liver to PH and may be important in the modulation of normal liver growth and repair.
β型转化生长因子（TGF-β）是一种由多种细胞类型产生的因子，在体外是肝细胞DNA合成的强效抑制剂。为了确定TGF-β是否能在体内影响肝细胞增殖，研究了其对大鼠肝脏部分切除术后（PH）肝脏再生反应的影响。猪血小板衍生的TGF-β1（0.5微克）在PH时及11小时后静脉注射，使PH后22小时参与DNA合成的肝细胞比例降低了67%，并使肝脏[3H]胸苷掺入率降低了50%。TGF-β2产生了类似的效果。在PH后11小时给予单剂量0.5微克的TGF-β1使肝脏[3H]胸苷掺入率降低了32%；4.5微克的TGF-β1或TGF-β2抑制DNA合成达88%，标记指数降低了86%。尽管在细胞周期的G1期晚期对PH后11小时给予的TGF-β敏感，但在PH时给予单剂量(0.5微克)在PH后22小时并未显著影响DNA合成。TGF-β的抑制作用是短暂的；在0小时和11小时用两剂0.5微克TGF-β处理的大鼠在PH后8天已完全恢复其原来的肝脏DNA量。每12小时给予0.5微克TGF-β1或TGF-β2，共5天，未能抑制肝脏DNA量的恢复。然而，TGF-β处理动物的核标记指数明显高于对照组。根据肝脏组织学以及葡萄糖、胰岛素样生长因子I和两种肝酶的血浆浓度判断，没有证据表明TGF-β具有细胞毒性。因此，TGF-β1和TGF-β2可逆地抑制肝脏对PH的增殖反应，可能在正常肝脏生长和修复的调节中起重要作用。
