title: Calcitonin gene-related peptide regulates the early phase of liver regeneration.
abstract: OBJECTIVE
  To investigate the expression of calcitonin gene-related peptide (CGRP) and its role in the liver regeneration process after 70% hepatectomy (Hx).
  
  
  METHODS
  Wistar rats were divided into eight groups based on time after Hx. Remnant liver samples were collected serially 0 h, 1 h, 6 h, 12 h, 1 d, 2 d, 7 d, and 14 d after Hx (n = 6 for each time point). The expression level of the calcitonin/CGRP gene in the remnant liver was measured. Western bolts and immunohistochemistry were performed to determine the levels of CGRP in the regenerating liver. Furthermore, CGRP8-37 (a CGRP receptor antagonist) was used to examine the role of CGRP during liver regeneration.
  
  
  RESULTS
  A marked upregulation of the calcitonin/CGRP gene was observed immediately after Hx, and the protein levels of CGRP in the liver, which were measured by western blot and immunohistochemistry, also rapidly increased after Hx. The liver regeneration rate was significantly attenuated by an administration of CGRP8-37 2 d after Hx. The mitotic index was evaluated by histologic examination 1 and 2 d after Hx and was also significantly lower in the CGRP8-37 group. In addition, CGRP8-37 treatment inhibited the phosphorylation of extracellular-signal regulated kinase 1/2. The levels of early response genes, such as c-fos, c-jun, and c-myc, were also downregulated by CGRP8-37.
  
  
  CONCLUSIONS
  The calcitonin/CGRP gene may have an important role in the early phase of liver regeneration after Hx.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Mizutani
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Kokuryo
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kawai
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyake
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000235:genetics / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006498:Hepatectomy; D007150:Immunohistochemistry; D008115:Liver Regeneration; D008297:Male; D010446:Peptide Fragments; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; C058636:calcitonin gene-related peptide (8-37); D002116:Calcitonin; D048049:Extracellular Signal-Regulated MAP Kinases; D015740:Calcitonin Gene-Related Peptide