Preserving hepatic artery flow during portal triad blood inflow occlusion improves remnant liver regeneration in rats after partial hepatectomy

Abstract Objective To investigate the mechanisms driving the interaction of platelets with liver sinusoidal endothelial cells (LSEC) during liver regeneration. Methods Platelets were tracked in vivo in mice by intravital confocal microscopy after partial hepatectomy. In vitro, we isolated highly pure mouse LSEC and analyzed their interactions with platelets, hepatic stellate cells (HSC), Kupffer cells and hepatocytes. Results Recruited platelets adhered to LSEC in vivo within the remnant liver segments following partial hepatectomy and were necessary for the interleukin 6 (IL-6) burst that occurred afterwards. In vitro, platelets were activated after incubation with LSEC and released transforming growth factor β1 (TGF-β1), which stimulated LSEC to secrete IL-6 (fold increase of 9.8±0.73 relative to baseline). Antibody-mediated neutralization of TGF-B1 or its downstream SMAD signalling pathway prevented the effects of activated platelets on LSEC. We also demonstrated that IL-6 released by LSEC stimulates HSC to produce hepatocyte growth factor (HGF) a main mitogen for hepatocytes. Conclusion Our results suggest that after hepatectomy, platelets initiate liver regeneration by interacting with LSEC and stimulate IL-6 release, which in turn stimulates HSC to produce HGF.

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Control of tissue carnitine contents: Effects of partial hepatectomy and liver regeneration on carnitine concentrations in liver and extrahepatic tissues of the rat

Bioscience Reports ◽

10.1007/bf01117440 ◽

1985 ◽

Vol 5 (1) ◽

pp. 47-55 ◽

Cited By ~ 5

Author(s):

Timothy J. French ◽

Anthony W. Goode ◽

Paul S. Schofield ◽

Mary C. Sugden

Keyword(s):

Liver Regeneration ◽

Partial Hepatectomy ◽

Surgical Removal ◽

Remnant Liver ◽

Liver Mass ◽

Liver Remnant ◽

Extrahepatic Tissues

The liver is the sole site of carnitine biosynthesis in the rat. However, the first 24 h after the surgical removal of two-thirds of the liver mass are not associated with depletion of carnitine either in the liver remnant or in a number of extrahepatic tissues with relatively short turnover times of carnitine (<24 h; heart, spleen, kidney). Dietary carnitine was not supplied. The results suggest that the capacity of the remnant liver for carnitine biosynthesis is sufficient to maintain tissue carnitine contents. Liver regeneration influenced the relative proportions of hepatic free and acylated carnitines in a manner compatible with changes in fat disposition in the proliferating tissue.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.268.5.g872 ◽

1995 ◽

Vol 268 (5) ◽

pp. G872-G878 ◽

Cited By ~ 5

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)

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