Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat.

Russell WE, Coffey RJ, Ouellette AJ, Moses HL
Proc Natl Acad Sci U S A. 1988 85 (14): 5126-30

PMID: 3164865 · PMCID: PMC281701 · 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.

MeSH Terms (15)

Alkaline Phosphatase Animals Aspartate Aminotransferases Blood Glucose DNA Growth Substances Hepatectomy Insulin-Like Growth Factor I Liver Liver Regeneration Male Peptides Rats Rats, Inbred Strains Transforming Growth Factors

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