Epidermal growth factor secreted from the salivary gland is necessary for liver regeneration

1995 ◽  
Vol 268 (5) ◽  
pp. G872-G878 ◽  
Author(s):  
D. E. Jones ◽  
R. Tran-Patterson ◽  
D. M. Cui ◽  
D. Davin ◽  
K. P. Estell ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Salivary Glands ◽  
Partial Hepatectomy ◽  
Cellular Proliferation ◽  
Remnant Liver ◽  
Epidermal Growth

Partial hepatectomy (PH) in rats induces a synchronized burst of DNA replication in the remnant liver that peaks at 24 h post-PH. We report here that removal of the major salivary glands before one-third and two-thirds PH prevents the proliferative response in the remaining liver. Twelve days after one-third PH, the remnant liver is 89% of the normal liver weight in nonsalivectomized rats but only 55% in salivectomized animals. This indicates that salivectomy does not merely delay the first round of cell division but that it prevents actual regeneration. Salivectomy alters the early protooncogene response to partial hepatectomy. In salivectomized rats, the characteristic peak of c-myc mRNA synthesis at 2-4 h after PH is significantly decreased compared with nonsalivectomized rats. The peak of DNA synthesis at 24 h after PH in salivectomized rats is also dramatically decreased. DNA synthesis as measured by [3H]thymidine incorporation into DNA of hepatic cells is decreased approximately 90% in salivectomized rats vs. nonsalivectomized rats 22-26 h after PH. Ligation of the venous drainage of the salivary gland results in the same inhibitory effect on DNA synthesis, indicating 1) that the salivary gland must release circulating factor(s), and 2) that the early increase in c-myc expression and the subsequent DNA synthesis, both of which reflect the stimulation of cellular proliferation in the regenerating liver, are induced by humoral factor(s) released from the salivary glands. Injection of exogenous epidermal growth factor (EGF) in salivectomized rats results in restoration of both the DNA synthetic and c-myc responses at levels characteristic of those of liver regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of epidermal growth factor on liver regeneration after partial hepatectomy in mice

1991 ◽  
Vol 128 (3) ◽  
pp. 425-431 ◽  
Author(s):  
S. Noguchi ◽  
Y. Ohba ◽  
T. Oka
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Dna Content ◽  
Sharp Peak ◽  
Submandibular Glands ◽  
Total Liver ◽  
Epidermal Growth

ABSTRACT The role of epidermal growth factor (EGF) in liver regeneration was studied in mice after partial hepatectomy. Two weeks before partial hepatectomy, mice were sham-operated (control) or sialoadenectomized (removal of submandibular glands) to reduce plasma EGF levels. Sialoadenectomized mice showed low plasma EGF levels (29·7 ±6·6 pmol/l; mean ± s.e.m.) compared with controls (66·0±8·3 pmol/l). After partial hepatectomy, sialoadenectomized mice were treated with or without a daily s.c. injection of 5 μg EGF and the rate of DNA synthesis in the regenerating liver was monitored by [125I]iododeoxyuridine uptake. Control mice showed a sharp peak of DNA synthesis at 48 h after partial hepatectomy while sialoadenectomized mice showed a delayed and broad peak at 84 h. Treatment of sialoadenectomized mice with EGF (5 μg/mouse per day) completely restored the pattern of DNA synthesis so that a sharp peak appeared at 48 h. The total liver DNA content of the control mice (79·1±2·5% of the preoperative level; mean ± s.e.m.) was significantly (P < 0·01) higher than that of the sialoadenectomized mice (65·2±3·0%) 3 days after partial hepatectomy, but this difference disappeared on day 7 when liver regeneration was almost completed in both groups. Treatment of sialoadenectomized mice with EGF increased total liver DNA content (78·2±2·9%) to that of control mice on day 3 after partial hepatectomy. In addition, normal mice showed a rapid increase in plasma EGF levels at 1–8 h after partial hepatectomy, whereas sialoadenectomized mice showed low plasma EGF levels throughout the course of the experiment. These results suggest that EGF derived from the submandibular glands plays a role in promoting the early stage of liver regeneration. Journal of Endocrinology (1991) 128, 425–431

Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

Hepatology ◽  
1988 ◽  
Vol 8 (5) ◽  
pp. 992-996 ◽  
Author(s):  
Peter Skov Olsen ◽  
Steen Boesby ◽  
Preben Kirkegaard ◽  
Kim Therkelsen ◽  
Thomas Almdal ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Epidermal Growth

Epidermal growth factor-mediated effects on equine vascular smooth muscle cells

1988 ◽  
Vol 255 (4) ◽  
pp. C447-C451 ◽  
Author(s):  
D. A. Grosenbaugh ◽  
M. S. Amoss ◽  
D. M. Hood ◽  
S. J. Morgan ◽  
J. D. Williams
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Vascular Smooth Muscle Cells ◽  
Cellular Proliferation ◽  
Epidermal Growth ◽  
Dose Dependent

Epidermal growth factor (EGF) receptor binding kinetics and EGF-mediated stimulation of DNA synthesis and cellular proliferation were studied in cultured vascular smooth muscle cells (VSMC) from the equine thoracic aorta. Binding studies, using murine 125I-labeled EGF, indicate the presence of a single class of high-affinity binding sites (apparent KD = 2.8 X 10(-11) M), with an estimated maximal binding capacity of 5,800 sites/cell. EGF stimulated [3H]thymidine uptake in confluent quiescent monolayers in a dose-dependent fashion, half-maximal stimulation occurring at 7.5 X 10(-11) M. Likewise, EGF-mediated cellular proliferation was dose dependent (50% effective dose = 5 X 10(-11) M) under reduced serum concentrations. Equine VSMC contain specific receptors for EGF, and EGF can stimulate DNA synthesis and proliferation in these cultured cells, which suggests that EGF may participate in the proliferative changes observed in equine distal digital peripheral vascular disease.

scholarly journals An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor-like repeat family stimulates DNA synthesis.

1995 ◽  
Vol 15 (1) ◽  
pp. 120-128 ◽  
Author(s):  
B Lecka-Czernik ◽  
C K Lumpkin ◽  
S Goldstein
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Cellular Proliferation ◽  
Werner Syndrome ◽  
Human Fibroblasts ◽  
Extracellular Proteins ◽  
Gene Transcript ◽  
Epidermal Growth ◽  
Novel Protein

We carried out subtractive enrichment of a cDNA library derived from mRNA of senescent human diploid fibroblasts (HDF) established from a subject with Werner syndrome of premature aging. By differential screening, we isolated an overexpressed cDNA sequence (S1-5) that codes for a novel protein containing epidermal growth factor (EGF)-like domains which match the EGF-like consensus sequences within several known extracellular proteins that play a role in cell growth, development, and cell signalling. S1-5 mRNA is overexpressed in Werner syndrome and senescent normal HDF, is induced by growth arrest of young normal cells, but is significantly decreased by high serum, conditions which promote cellular proliferation. Paradoxically, microinjection into young HDF of two different lengths of S1-5 mRNA, containing different putative AUG translational start sites, consistently stimulated rather than inhibited DNA synthesis by an apparent autocrine/paracrine mechanism. Thus, the S1-5 gene product may represent a negative and/or positive factor whose ultimate activity is modulated by the cell environment as occurs with other members of EGF-like family.

Stimulatory Effect of Epidermal Growth Factor on Liver Regeneration after Partial Hepatectomy in Rats

1992 ◽  
Vol 27 (5) ◽  
pp. 372-374 ◽  
Author(s):  
T. N. Rasmussen ◽  
P. E. JøSrgensen ◽  
T. Almdal ◽  
P. Kirkegaard ◽  
P. Skov Olsen
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Epidermal Growth

scholarly journals Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+.

1984 ◽  
Vol 98 (3) ◽  
pp. 1082-1089 ◽  
Author(s):  
C P Burns ◽  
E Rozengurt
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Cellular Proliferation ◽  
Weak Acid ◽  
Mechanisms Of Action ◽  
Epidermal Growth ◽  
Reversible Time ◽  
Stimulation Of

Initiation of DNA synthesis in confluent quiescent 3T3 cell cultures stimulated by epidermal growth factor (EGF), vasopressin, and insulin was abolished by removing extracellular Na+. The inhibition was reversible, time- and Na+-concentration-dependent, and not due to an effect on binding or internalization of 125I-EGF. Stimulation by combinations of other growth factors with different mechanisms of action was also affected by decreasing extracellular Na+, but with different half-maximal Na+ concentrations. When choline was used as an osmotic substitute for Na+, the decrease in DNA synthesis was correlated with the decrease in intracellular K+. In contrast, when sucrose was used there was stimulation of the Na+-K+ pump and maintenance of intracellular K+ that resulted in a somewhat higher rate of DNA synthesis at lowered extracellular Na+ compared to choline. Mitogenesis induced by epidermal growth factor, vasopressin, and insulin led to cytoplasmic alkalinization as determined by an increase in uptake of the weak acid 5,5-dimethyloxazolidine-2,4-dione. Experimental decrease in extracellular Na+ blocked this cellular alkalinization. Therefore, under some conditions the supply of extracellular Na+ may limit cellular proliferation because of a reduction in the provision of Na+ to the Na+/H+ antiport and resultant failure of alkalinization. We conclude that Na+ flux and its effect on intracellular K and pH has a major role in the complex system that regulates proliferation.

Role of heparin-binding epidermal growth factor–like growth factor as a hepatotrophic factor in rat liver regeneration after partial hepatectomy

Hepatology ◽  
1995 ◽  
Vol 22 (5) ◽  
pp. 1584-1590 ◽  
Author(s):  
Shinichi Kiso ◽  
Sumio Kawata ◽  
Shinji Tamura ◽  
Shigeki Higashiyama ◽  
Nobuyuki Ito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Heparin Binding ◽  
Rat Liver Regeneration ◽  
Epidermal Growth
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