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

Journal Article · Fri Jul 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.14.5126· OSTI ID:5471748

Russell, W E; Coffey, Jr, R J; Ouellette, A J; Moses, H L ^[1]

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1. Massachusetts General Hospital, Boston (USA)

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, 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 ({sup 3}H)thymidine incorporation by 50%. TGF-{beta}2 produced a similar effect. Although sensitive to TGF-{beta} administered 11 hr after PH, late in the G{sub 1} phase of the cell cycle, a single does 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. 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.

• OSTI ID: 5471748
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:14; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DNA REPLICATION
INHIBITION
GROWTH FACTORS
BIOLOGICAL EFFECTS
LIVER
CELL PROLIFERATION
BLOOD PLATELETS
HEPATECTOMY
IODINE 125
RATS
SWINE
THYMIDINE
TRITIUM COMPOUNDS
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DOMESTIC ANIMALS
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
MAMMALS
MATERIALS
MEDICINE
MITOGENS
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
RODENTS
SURGERY
VERTEBRATES
550301* - Cytology- Tracer Techniques