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

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

1995 ◽  
Vol 268 (5) ◽  
pp. G872-G878 ◽  
Author(s):  
D. E. Jones ◽  
R. Tran-Patterson ◽  
D. M. Cui ◽  
D. Davin ◽  
K. P. Estell ◽  
...  

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)


Hepatology ◽  
1988 ◽  
Vol 8 (5) ◽  
pp. 992-996 ◽  
Author(s):  
Peter Skov Olsen ◽  
Steen Boesby ◽  
Preben Kirkegaard ◽  
Kim Therkelsen ◽  
Thomas Almdal ◽  
...  

1992 ◽  
Vol 27 (5) ◽  
pp. 372-374 ◽  
Author(s):  
T. N. Rasmussen ◽  
P. E. JøSrgensen ◽  
T. Almdal ◽  
P. Kirkegaard ◽  
P. Skov Olsen

Hepatology ◽  
1995 ◽  
Vol 22 (5) ◽  
pp. 1584-1590 ◽  
Author(s):  
Shinichi Kiso ◽  
Sumio Kawata ◽  
Shinji Tamura ◽  
Shigeki Higashiyama ◽  
Nobuyuki Ito ◽  
...  

2021 ◽  
pp. 739-760

BACKGROUND/AIMS: Liver is considered as the vital organ in the body as it performs various essential functions. Following an injury to the liver, the repair process even though initially beneficial becomes pathogenic when it is not controlled appropriately. Extensive accumulation of extracellular matrix (ECM) components can ultimately lead to cirrhosis and liver failure. Thus, the ideal strategy to treat a liver injury is to generate new hepatocytes replacing damaged cells without causing excessive ECM deposition. The objective of this study was to evaluate the potential of mesenchymal stem cells, conditioned media and murine epidermal growth factor (m-EGF) in liver regeneration following partial hepatectomy in a rat model. METHODS: The animals were anaesthetized and a midline laparotomy was done. The liver was exposed and the left lateral and median lobes were ligated and resected out (about 65-70% of total liver mass). The muscles and skin were sutured in routine fashion and thus the rat model of partial hepatectomy was prepared. The animal models were equally distributed into 4 different groups namely A, B, C and D and treated with PBS, conditioned media, mesenchymal stem cells and epidermal growth factor respectively. The liver regeneration was assessed based on clinical, haemato-biochemical, colour imaging, histopathological and immune-histochemical parameters. RESULTS: Partial hepatectomy model with surgical removal of 65-70% liver lobe was standardized and successfully used in this study. Alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, transaminases were significantly higher (P<0.05) in group A indicating that the liver damage was not restored properly. Colour digital imaging, histopathological and immune-histochemistry observations revealed that a better liver regeneration was observed in groups C and D, followed by groups B and A. Regeneration coefficient calculated based on liver weight was higher in groups C and D as compared to group A. CONCLUSION: Rat bone marrow-derived mesenchymal stem cells were found to induce hepatocytes proliferation; whereas EGF induced more angiogenesis. Conditioned media was not as effective as stem cells and EGF in liver tissue repair.


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