TYPE-BETA TRANSFORMING GROWTH-FACTOR REVERSIBLY INHIBITS THE EARLY PROLIFERATIVE RESPONSE TO PARTIAL-HEPATECTOMY IN THE RAT
TYPE-BETA TRANSFORMING GROWTH-FACTOR REVERSIBLY INHIBITS THE EARLY PROLIFERATIVE RESPONSE TO PARTIAL-HEPATECTOMY IN THE RAT
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DOI：
10.1073/pnas.85.14.5126
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发表时间：
1988-07-01
影响因子：
11.1
通讯作者：
MOSES, HL
中科院分区：
文献类型：
--
作者：
RUSSELL, WE;COFFEY, RJ;MOSES, HL
输入 .beta。转化生长因子(TGF-β)是许多细胞类型产生的因子，是体外肝细胞DNA合成的有效抑制剂。确定TGF-.beta是否存在。可以影响体内肝细胞增殖，研究了其对大鼠肝脏对部分肝切除术（PH）的再生反应的影响。猪血小板来源的TGF-β1(0.5μg)在PH时和11小时后静脉内施用，使PH后22小时参与DNA合成的肝细胞分数减少67%，并抑制肝脏[3H]胸苷掺入率50%。 TGF-β2产生类似的效果。 PH后11小时给予单剂0.5μg TGF-β1，使肝脏[3H]胸苷掺入减少32%； 4.5μg TGF-β1或TGF-β2抑制DNA合成88％和标记指数86％。尽管对 TGF-β 敏感。在PH后11小时施用，在细胞周期的G1期晚期，在PH时施用的单剂量0.5μg不会显着影响PH后22小时的DNA合成。 TGF-β的抑制作用。是短暂的；用两次 0.5-.mu.g 剂量的 TGF-β 治疗的大鼠。 PH 后 8 天，0 小时和 11 小时完全恢复了其原始肝脏 DNA 质量。每12小时施用0.5μg TGF-β1或TGF-β2持续5天未能抑制肝DNA质量的恢复。然而，TGF-β处理的动物的核标记指数显着高于对照。根据肝脏组织学和葡萄糖、胰岛素样生长因子I和两种肝酶的血浆浓度测定，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，并且在正常肝脏生长和修复的调节中可能是重要的。
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 .mu.g), 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 .mu.g of TGF-.beta.1 given 11 hr after PH reduced liver [3H]thymidine incorporation by 32%; 4.5 .mu.g 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 .mu.g 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-.mu.g doses of TGF-.beta. at 0 and 11 hr had completely restored their original liver DNA mass 8 dyas after PH. Administration of 0.5 .mu.g 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.