Alterations in platelet-derived growth factor expression in the pathophysiology of necrotizing enterocolitis

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-alpha and PDGFR-beta, 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-alpha, 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-beta, 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. (C) 2015 Elsevier Inc. All rights reserved.