scholarly journals Native and recombinant human hepatocyte growth factors are highly potent promoters of DNA synthesis in both human and rat hepatocytes.

1991 ◽  
Vol 87 (5) ◽  
pp. 1853-1857 ◽  
Author(s):  
A J Strain ◽  
T Ismail ◽  
H Tsubouchi ◽  
N Arakaki ◽  
T Hishida ◽  
...  
1996 ◽  
Vol 271 (3) ◽  
pp. C721-C727 ◽  
Author(s):  
H. T. Sponsel ◽  
P. S. Guzelian ◽  
S. E. Brown ◽  
R. Breckon ◽  
C. Ray ◽  
...  

The mechanism(s) whereby hepatocytes restore denuded areas remains unknown. We therefore studied the recovery of denuded areas made in monolayers of primary cultures of rat hepatocytes. Minimal recovery occurred in cells plated on plastic. Plating on Matrigel produced modest recovery (25% at 24 h), whereas plating on a type I collagen substrate resulted in > 70% recovery at 24 h. The rate of recovery on collagen could be attenuated by a monoclonal antibody directed against the extracellular domain of the beta 1-integrin subunit. Monoclonal antibodies directed against CD44 (the hyaluron receptor) and E-cadherin did not influence the rate of recovery. Recovery could be stimulated, in a dose-dependent fashion, by epidermal and hepatocyte growth factors. The effects of epidermal and hepatocyte growth factors to promote recovery occurred in the absence of 5-bromo-2'-deoxyuridine uptake, suggesting a proliferation-independent mechanism. Transforming growth factor-beta 1 inhibited recovery. Exposure to selected cytokines (interleukins 1 and 2), an adenine nucleotide [adenosine 5'-O-(3-thiotriphosphate)], adenosine, pertussis toxin, and selected agents that bind to fibronectin and other matrix component adhesive sites (heparin and the RGD peptide) did not influence the rate of recovery of hepatocytes. However, the peptide DGEA, which can bind to collagen adhesive sites, attenuated recovery. These studies demonstrate that primary cultures of rat hepatocytes require a particular type of extracellular matrix to renew denuded areas and that the beta 1-integrin subunit may be involved in this recovery process. Hepatocyte recovery of denuded areas can be modulated by growth factors in both a stimulatory (epidermal and hepatocyte growth factors) and an inhibitory (transforming growth factor-beta 1) fashion.


1995 ◽  
Vol 109 (4) ◽  
pp. 1068-1077 ◽  
Author(s):  
Yoshikazu Kinoshita ◽  
Hirohisa Nakata ◽  
Sazzad Hassan ◽  
Masakyo Asahara ◽  
Chiharu Kawanami ◽  
...  

1996 ◽  
Vol 20 (s9) ◽  
pp. 330A-334A ◽  
Author(s):  
Katsuhisa Saso ◽  
Katsuyoshi Higashi ◽  
Tomoyuki Nomura ◽  
Makoto Hoshino ◽  
Makoto Ito ◽  
...  

1988 ◽  
Vol 91 (4) ◽  
pp. 549-553
Author(s):  
P. Little ◽  
G.G. Skouteris ◽  
M.G. Ord ◽  
L.A. Stocken

Serum obtained from partially hepatectomized rats 1, 3 or 24 h after operation was more effective in stimulating DNA synthesis in primary adult rat hepatocytes than serum from sham-operated rats; exposure to the serum for 2 h was sufficient to promote growth. Serum from the partially hepatectomized rats contained elevated levels of PGE2 and PGF2 alpha; it promoted hepatocytes to release prostaglandins into their culture medium. Growth-promoting effects of the serum and its capacity to elicit prostaglandin release into the culture medium were inhibited by 0.1 mM-indomethacin or 1 mM-aspirin. 0.1 mM-indomethacin also prevented DNA synthesis if the inhibitor were added 4 h after growth had been initiated by serum from partially hepatectomized rats, suggesting that prostaglandins continue to be important for the maintenance of hepatocyte growth for at least 6 h.


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