title: Expression of transforming growth factor beta1, beta2, and beta3 in chronic, cancer-associated, obstructive pancreatitis.
abstract: BACKGROUND
  Myofibroblasts are considered to play central roles in pancreatic fibrosis. The potent fibrogenic capacities of transforming growth factor betas (TGF-betas) have been emphasized in vitro and in animal studies. However, the roles of TGF-betas in human chronic pancreatitis have not been fully clarified.
  
  
  OBJECTIVE
  To investigate whether expressions of TGF-betas are related to myofibroblast distribution in chronic, cancer-associated, obstructive pancreatitis (COP).
  
  
  METHODS
  Histopathologic studies using hematoxylin-eosin and Elastica-Masson trichrome and immunohistochemical studies using antibodies against alpha-smooth muscle actin (SMA); CD68; TGF-beta1, -beta2, and -beta3; and TGF-beta soluble receptor type II were performed in 19 COP cases and 6 controls. By classifying COP tissues into 3 fibrosis phases by the amount of collagen deposits, immunoreactivities for TGF-betas, histopathologic changes, and myofibroblast distribution were examined for each fibrosis phase.
  
  
  RESULTS
  Six cases were categorized in the early stage of fibrosis, 8 in the intermediate stage, and 5 in the advanced stage. Immunoreactivities for all 3 isoforms of TGF-beta were observed in occasional myofibroblasts. In the early and intermediate stages, TGF-beta1-expressing macrophages and neutrophils were distributed in the midst of myofibroblasts. TGF-beta2 and TGF-beta3 expressions were observed in ductal structures, sometimes even in sites where no or few myofibroblasts were seen. TGF-beta soluble receptor type II was immunoreactive for myofibroblasts, endothelium, and ductal structures.
  
  
  CONCLUSIONS
  All 3 isoforms of TGF-betas may contribute to fibrosis in COP. Macrophages and neutrophils may be sources of fibrogenic TGF-beta1. Infiltration of these cells appears to play an important role in the progression of COP fibrosis.
authors.affiliation: Department of Pathology I, Juntendo University, School of Medicine, Tokyo, Japan. yfuku@med.juntendo.ac.jp
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukumura
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Keiko
authors.initials: K
authors.lastname: Mitani
authors.forename: Kanae
authors.initials: K
authors.lastname: Karita
authors.forename: Koichi
authors.initials: K
authors.lastname: Suda
mesh_terms: D000368:Aged; D002908:Chronic Disease; D003251:Constriction, Pathologic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010183:Pancreatic Ducts; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016212:Transforming Growth Factor beta