title: Alterations in platelet-derived growth factor expression in the pathophysiology of necrotizing enterocolitis.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC) involves impaired ileal blood flow due to alterations in vascular tone control and intestinal angiogenesis. Platelet-derived growth factor (PDGF) is a mediator of normal angiogenesis in intestinal epithelium. We hypothesized that gene dysregulation during experimental NEC results in altered PDGF expression.
  
  
  METHODS
  Sprague-Dawley rats were randomized to groups by litter. Controls were delivered vaginally and dam-fed. NEC groups were delivered prematurely by cesarean section and subjected to an established NEC protocol. Ileum was obtained at 0, 12, 24, 48, 72, and 96 h of life from all animals (N = 108 animals). Western blot analysis was carried out for every time point, and samples were evaluated by immunohistochemistry. Antibodies against PDGF-A, PDGF-B, and their receptors, PDGFR-α and PDGFR-β, were used. Statistical analysis was performed using two-way analysis of variance with a priori P < 0.05.
  
  
  RESULTS
  Ileal PDGF-A concentration was higher in controls versus NEC from 24-96 h of life. Its receptor, PDGFR-α, was low in concentration in both groups at all time points. PDGF-B concentration was increased in controls at 24 and 72 h of life but decreased at the 48-h mark. Its receptor, PDGFR-β, was also low in both groups at 12 and 24 h but increased in controls at 48 and 72 h.
  
  
  CONCLUSIONS
  These data support our hypothesis that PDGF and PDGF receptor expression are altered in experimental NEC. Dysregulation of PDGF during intestinal maturation could contribute to the development of NEC. Further investigation into this pathway could yield new therapeutic targets for this devastating disease.
authors.affiliation: Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky; Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky. Electronic address: jashep04@louisville.edu.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Shepherd
authors.affiliation: University of Louisville Medical School, University of Louisville, Louisville, Kentucky.
authors.forename: Eric
authors.initials: E
authors.lastname: Stamper
authors.affiliation: Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky; Robley Rex Veterans Affairs Medical Center at Louisville, Louisville, Kentucky.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Matheson
authors.affiliation: University of Louisville Medical School, University of Louisville, Louisville, Kentucky.
authors.forename: Laura
authors.initials: L
authors.lastname: Galganski
authors.affiliation: Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky; Robley Rex Veterans Affairs Medical Center at Louisville, Louisville, Kentucky.
authors.forename: R Neal
authors.initials: RN
authors.lastname: Garrison
authors.affiliation: Department of Pathology, University of Louisville, Louisville, Kentucky.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Madden
authors.affiliation: Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Downard
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000098:blood supply*; D055806:Microvessels / Q000254:growth & development* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Intestinal ischemia; Necrotizing enterocolitis; Platelet-derived growth factor