title: Connective tissue growth factor is involved in pancreatic repair and tissue remodeling in human and rat acute necrotizing pancreatitis.
abstract: OBJECTIVE
  To analyze the involvement of connective tissue growth factor (CTGF) in the transforming growth factor-beta (TGF-beta) pathway during acute necrotizing pancreatitis (ANP) in humans and rats.
  
  
  BACKGROUND
  Connective tissue growth factor is involved in several fibrotic diseases and has a critical role in fibrogenesis and tissue remodeling after injury.
  
  
  METHODS
  Normal human pancreas tissue samples were obtained through an organ donor program from five individuals without a history of pancreatic disease. Human ANP tissues were obtained from eight persons undergoing surgery for this disease. In rats, ANP was induced by intraductal infusion of taurocholate. The expression of CTGF was studied by Northern blot analysis, in situ hybridization, and immunohistochemistry in both human and rat pancreatic tissue samples.
  
  
  RESULTS
  Northern blot analysis revealed enhanced CTGF mRNA expression in human ANP tissue samples compared with normal controls. In addition, a concomitant increase in TGF-beta1 was present. By in situ hybridization, CTGF mRNA was localized in the remaining acinar and ductal cells and in fibroblasts. In regions of intense damage adjacent to areas of necrosis, CTGF mRNA signals were most intense. Inflammatory cells were devoid of any CTGF mRNA signals. By immunohistochemistry, CTGF protein was localized at high levels in the same cell types as CTGF mRNA. In ANP in rats, concomitantly enhanced mRNA levels of CTGF, TGF-beta1, and collagen type 1 were present, with a biphasic peak pattern on days 2 to 3 and day 7 after induction of ANP.
  
  
  CONCLUSIONS
  These data indicate that CTGF participates in tissue remodeling in ANP. The expression of CTGF predominantly in the remaining acinar and ductal cells indicates that extracellular matrix synthesis after necrosis is at least partly regulated by the remaining pancreatic parenchyma and only to a minor extent by inflammatory cells. Blockage of CTGF, a downstream mediator of TGF-beta in fibrogenesis, might be useful as a target to influence and reduce fibrogenesis in this disorder.
authors.affiliation: Department of General Surgery, University of Heidelberg, Germany.
authors.forename: Fabio F
authors.initials: FF
authors.lastname: di Mola
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Erick
authors.initials: E
authors.lastname: Riesle
authors.forename: Alexander
authors.initials: A
authors.lastname: Koliopanos
authors.forename: Peter
authors.initials: P
authors.lastname: Büchler
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zhu
authors.forename: David R
authors.initials: DR
authors.lastname: Brigstock
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000328:Adult; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D055513:Connective Tissue Growth Factor; D018076:DNA, Complementary / Q000032:analysis; D003627:Data Interpretation, Statistical; D005260:Female; D006133:Growth Substances / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D019283:Pancreatitis, Acute Necrotizing / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000502:physiology
chemical_list: C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D002352:Carrier Proteins; D018076:DNA, Complementary; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor