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

Journal Article · Fri Jul 01 04:00:00 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]

---

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

Related Subjects

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