title: The platelet-activating receptor C-type lectin receptor-2 plays an essential role in liver regeneration after partial hepatectomy in mice.
abstract: Essentials Regeneration role of C-type lectin receptor-2 (CLEC-2) after 70% hepatectomy (HPx) was investigated. Wild-type or CLEC-2 deleted from platelets of chimeric mice (flKO) underwent HPx. The liver/body weight ratio was significantly lower in the flKO than in the wild-type. CLEC-2 plays an essential role in liver regeneration after HPx.
  
  
  
  Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice. Materials and methods Irradiated chimeric mice transplanted with fetal liver cells from wild-type (WT) mice, CLEC-2-deleted (KO) mice or mice with CLEC-2 deleted specifically from platelets (flKO) were generated. Mice underwent 70% partial hepatectomy (PH). Immunohistochemical staining was performed to investigate the expression of the endogenous ligand for CLEC-2, podoplanin. The accumulation of platelets in the liver was also quantified. The hepatic expression of the IL-6/gp130 and STAT3, Akt and ERK1/2 was also examined. Results The liver/body weight ratio and expression of all cell proliferation markers were significantly lower in the flKO group than in the WT group. The expression of phosphorylated (p) Akt and pERK1/2 was similar in the WT and flKO groups. On the other hand, the expression of pSTAT3 and IL-6 was significantly stronger in the WT group than in the flKO group. The expression of podoplanin was detected in the hepatic sinusoids of both groups. However, the extent to which platelets accumulated in hepatic sinusoids was significantly less in the flKO group than in the WT group. Conclusion CLEC-2 was involved in hepatic regeneration after liver resection and CLEC-2-related liver regeneration was attributed to the interaction between platelets and sinusoidal endothelial cells.
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kono
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki-Inoue
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Inoue
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Furuya
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hirayama
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Akazawa
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakata
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tsukiji
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010766:Phosphorylation; D015539:Platelet Activation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D019938:Cyclin D1; D050822:Cytokine Receptor gp130; D048049:Extracellular Signal-Regulated MAP Kinases; D015850:Interleukin-6; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C529518:CLEC-2 protein, mouse; C530105:Ccnd1 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C494200:Il6st protein, mouse; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse; C467480:vascular endothelial growth factor A, mouse
keywords: hepatectomy; knockout mouse; liver regeneration; platelet; serotonin