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Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats

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World Journal of Gastroenterology 2005年第46期11卷 7254-7260页

作者： Hiroaki Shimizu Noboru Mitsuhashi Masayuki Ohtsuka Hiroshi Ito Fumio Kimura Satoshi Ambiru akira togawa Hiroyuki Yoshidome Atsushi Kato Masaru Miyazaki Department of General Surgery Graduate School of Medicine Chiba University Chiba 260-0856 Japan

AIM： To study the regulatory mechanisms of sinusoida regeneration after partial hepatectomy. METHODS： We invesldgated the expression of angiopoietin （Ang）-1, Ang-2, Tie-2, and vascular endothelial growth factor （VEGF） in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction （RT- PCR） using a LightCycler （Roche Diagnostics） and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells （hepatocytes, sinusoidal endothelial cell （SEC）, Kupffer cell, and hepatic stellate cells （HSC）） from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation, to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen （PCNA） staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling （TUNEL） assay, respectively. RESULTS： VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2 was found in the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h. CONCLUSION： Ang-Tie system, together with VEGF, plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.

关键词： Vascular endothelial cell growth factor Angiopoietin Sinusoidal endothelial cell Hepatectomy Liver regeneration

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Reduced hemoglobin and increased C-reactive protein are associated with upper gastrointestinal bleeding

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World Journal of Gastroenterology 2014年第5期20卷 1311-1317页

作者： Minoru Tomizawa Fuminobu Shinozaki Rumiko Hasegawa akira togawa Yoshinori Shirai Noboru Ichiki Yasufumi Motoyoshi Takao Sugiyama Shigenori Yamamoto Makoto Sueishi Department of Gastroenterology National Hospital Organization Shimoshizu Hospital Yotsukaido City Department of Radiology National Hospital Organization Shimoshizu Hospital Yotsukaido City Department of Surgery National Hospital Organization Shimoshizu Hospital Yotsukaido City Department of Neurology National Hos- pital Organization Shimoshizu Hospital Yotsukaido City Department of Rheumatology National Hospital Organization Shimoshizu Hospital Yotsukaido City Department of Pediatrics National Hospital Organization Shimoshizu Hospital Yotsukaido City

AIM: To investigate the early upper gastrointestinal endoscopy (endoscopy) significantly reduces mortality resulting from upper gastrointestinal (GI) bleeding.

关键词： Receiver operating characteristic Area under curve Sensitivity Specificity Gastrointestinal bleeding

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

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World Journal of Gastroenterology 2006年第13期12卷 2053-2059页

作者： Hironobu Makino Hiroaki Shimizu Hiroshi Ito Fumio Kimura Satoshi Ambiru akira togawa Masayuki Ohtsuka Hiroyuki Yoshidome Atsushi Kato Hideyuki Yoshitomi Shigeaki Sawada Masaru Miyazaki Department of General Surgery Graduate School of Medicine Chiba UniversityChibaJapan

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-β1 （TGF-β1） 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 e-smooth muscle actin （α-SNA） 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 bUiary drainage in BO rats or sham-operated rats. RESULTS： Hepatic TGF-β1 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-β1 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 （α-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-β1 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-β1 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.

关键词： Biliary obstruction Liver regeneration Hepatocyte growth factor Transforming growth factor-β Hepatic stellate cells Hepatectomy

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