Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Apr 7;12(13):2053-9.
doi: 10.3748/wjg.v12.i13.2053.

Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy

Hironobu Makino  1 , Hiroaki Shimizu, Hiroshi Ito, Fumio Kimura, Satoshi Ambiru, Akira Togawa, Masayuki Ohtsuka, Hiroyuki Yoshidome, Atsushi Kato, Hideyuki Yoshitomi, Shigeaki Sawada, Masaru Miyazaki
Affiliations

Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy

Hironobu Makino et al. World J Gastroenterol. .

Abstract

Aim: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy.

Methods: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and alpha-smooth muscle actin (alpha-SMA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal biliary drainage in BO rats or sham-operated rats.

Results: Hepatic TGF-beta1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-beta1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (alpha-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-beta1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats.

Conclusion: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-beta1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A: Hepatocyte growth factor (HGF); B: c-Met; C: vascular endothelial growth factor (VEGF); D: transforming growth factor-β1 (TGF-β1) mRNA expression in rat liver at 14 and 21 d after biliary obstruction (BO) and sham-operation (sham). (aP < 0.05 vs sham-operated control, bP < 0.03 vs sham-operated control). Results are expressed as mean ± SD of n = 10 for each period in each group.
Figure 2
Figure 2
Hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGF-β1) mRNA expression in isolated rat liver cells (H: hepatocytes; SECs: sinusoidal endothelial sells; KC: Kupffer cells; HSCs: Hepatic stellate cells) 14 d after biliary obstruction (BO).
Figure 3
Figure 3
Immunohistochemical staining for desmin A: 14 d after sham operation; B: 14 d after biliary obstruction (BO); C: 21 d after biliary obstruction. Immunohistochemical staining for α-smooth muscle actin (α-SMA); D: 14 d after sham operation; E: 14 d after biliary obstruction.
Figure 4
Figure 4
A: Changes in regenerating liver weight ratio after 70% partial patectomy (PH) in the sham-operated (sham) rats and the biliary obstructed (BO) rats (aP <0.05 between the BO + PH group and the sham + PH group). Results are expressed as mean ± SD of n = 10 for each period in each group. B: Changes in the hepatocyte PCNA labeling index after 70% hepatectomy (PH) in the sham-operated (sham) rats and the biliary obstructed (BO) rats (1P < 0.03 between the BO + PH group and the sham + PH group). Results are expressed as mean ± SD of n = 10 for each period in each group.
Figure 5
Figure 5
Changes in A: hepatocyte growth factor (HGF); B: c-Met; C: vascular endothelial growth factor (VEGF); D: transforming growth factor-β1 (TGF-β1) mRNA expression after partial hepatectomy (PH) in the sham-operated (sham) rats and the biliary obstructed (BO) rats (aP <0.05 between the BO + PH group and the sham + PH group). Results are expressed as mean ± SD of n = 10 for each period in each group.
See this image and copyright information in PMC

References

    1. Miyazaki M, Ito H, Nakagawa K, Ambiru S, Shimizu H, Shimizu Y, Kato A, Nakamura S, Omoto H, Nakajima N, et al. Aggressive surgical approaches to hilar cholangiocarcinoma: hepatic or local resection. Surgery. 1998;123:131–136. - PubMed
    1. Bengmark S, Ekberg H, Evander A, Klofver-Stahl B, Tranberg KG. Major liver resection for hilar cholangiocarcinoma. Ann Surg. 1988;207:120–125. - PMC - PubMed
    1. Boerma EJ. Research into the results of resection of hilar bile duct cancer. Surgery. 1990;108:572–580. - PubMed
    1. Aronson DC, Chamuleau RA, Frederiks WM, Bosman DK, Oosting J. The effect of extrahepatic cholestasis on liver regeneration after partial hepatectomy in the rat. Liver. 1995;15:242–246. - PubMed
    1. Mizuno S, Nimura Y, Suzuki H, Yoshida S. Portal vein branch occlusion induces cell proliferation of cholestatic rat liver. J Surg Res. 1996;60:249–257. - PubMed