title: Immunohistochemical expression of FGF-2, PDGF-A, VEGF and TGF beta RII in the pancreas in the course of ischemia/reperfusion-induced acute pancreatitis.
abstract: Acute pancreatitis leads to pancreatic damage followed by subsequent regeneration. The aim of our study was to evaluate the presence of growth factors in the course of spontaneous pancreatic regeneration after ischemia/reperfusion (I/R)-induced pancreatitis.
  
  
  METHODS
  In rats, I/R was evoked by clamping of splenic artery for 30 min followed by reperfusion. Rats were sacrificed 1, 5, 12 h or 1, 2, 3, 5, 7, 9 or 21 days after removal of vascular clips. Pancreatic blood flow (PBF), plasma lipase, interleukin-1beta (IL-1beta), interleukin-10, pancreatic cells proliferation and morphological signs of pancreatitis were determined. Pancreatic presence of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta type II receptor (TGFbeta RII) was detected by immunohistochemisty.
  
  
  RESULTS
  Exposure to I/R led to the development of acute necrotizing pancreatitis followed by regeneration. Morphological features showed maximal pancreatic damage between the 1(st) and 2(nd) day of reperfusion. It was correlated with a maximal increase in plasma lipase, and pro-inflammatory IL-1beta concentration, as well as, a reduction in PBF and pancreatic DNA synthesis. I/R increased FGF-2 content in pancreatic acinar cells between the 12(th) and 24(th) h, and between 5(th) and 9(th) day of reperfusion. At the 2(nd) day the presence of FGF-2 in pancreatic acinar cells was reduced. After I/R PDGF-A appeared in pancreatic vessels from the 12(th) h to 5 (th) day of reperfusion. PDGF-A was not observed in pancreatic acinar cells in the control or in I/R group. In pancreatic ducts, the presence of PDGF-A was reduced between the 1(st) and 3(rd), and between 7(th) and 9(th) day of reperfusion. In acinar cells, VEGF content was increased after I/R at the time between the 1(st) and 24(th) h, and between 3(rd) and 7(th) day of reperfusion. At the 2(nd) day of reperfusion, VEGF was not detected in the pancreatic acinar cells. Moreover, VEGF was found in the inflammatory infiltration, in the tubular complexes between the 2(nd) and 5(th) day, and in granulation tissue at the 9(th) day of reperfusion. In pancreatic acinar cells, I/R caused an increase in TGFbeta RII presence between the 5(th) and 24(th) h, and between 7(th) and 9(th) day of reperfusion. Between the 2(nd) and 5(th) day of reperfusion the acinar presence of TGFbeta RII was reduced. In the pancreatic ducts, the presence of TGFbeta RII was increased after I/R from the 1(st) h to 9(th) day of observation. Four weeks after induction of acute pancreatitis, the pancreatic regeneration was completed and the presence of growth factors tested returned to control value.
  
  
  CONCLUSIONS
  The presence of FGF, VEGF, PDGF-A and TGFbeta RII is modified in the course of I/R-induced acute pancreatitis. Maximal content of FGF, VEGF and TGFbeta RII has been observed in early stage of pancreatic regeneration suggesting the involvement these factors in pancreatic recovery.
authors.affiliation: Department of Physiology, Jagiellonian University Medical School, 16 Grzegórzecka Street, 31-531 Kraków, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Warzecha
authors.forename: A
authors.initials: A
authors.lastname: Dembiński
authors.forename: P
authors.initials: P
authors.lastname: Ceranowicz
authors.forename: M
authors.initials: M
authors.lastname: Dembiński
authors.forename: P
authors.initials: P
authors.lastname: Kownacki
authors.forename: S J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: R
authors.initials: R
authors.lastname: Tomaszewska
authors.forename: J
authors.initials: J
authors.lastname: Stachura
authors.forename: W
authors.initials: W
authors.lastname: Hładki
authors.forename: W W
authors.initials: WW
authors.lastname: Pawlik
mesh_terms: D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D010179:Pancreas / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism; D010195:Pancreatitis / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017208:Rats, Wistar; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D015427:Reperfusion Injury / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D010982:Platelet-Derived Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II