title: Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model.
abstract: BACKGROUND
  The aim of this study was to investigate the effects of human β-defensin-3 (hBD3) on intestinal wound healing and in a neonatal rat model of necrotizing enterocolitis (NEC).
  
  
  METHODS
  Enterocyte migration and proliferation were detected in vitro and in vivo. The role of chemokine receptor CCR6 and its downstream signaling pathway was assessed. Newborn Sprague-Dawley rats were randomly divided into four groups: Control+NS, Control+hBD3, NEC+NS, and NEC+hBD3. Body weight, histological score, survival time, cytokines expression, and mucosal integrity were evaluated.
  
  
  RESULTS
  hBD3 could stimulate enterocyte migration, but not proliferation, both in cultured enterocytes and in the NEC model. Neutralizing antibody and small interfering RNA confirmed this stimulatory effect was mediated by CCR6. Furthermore, hBD3 induced Rho activation, myosin light chain 2 phosphorylation, and F-actin accumulation. The bactericidal activity of hBD3 was maintained throughout a broad pH range. Strikingly, hBD3 administration decreased the incidence of NEC, increased the survival rate, and reduced the severity of NEC. Moreover, hBD3 reduced the proinflammatory cytokines expression in ileum and serum and preserved the intestinal barrier integrity.
  
  
  CONCLUSIONS
  This study provided evidence that the antimicrobial peptide hBD3 might participate in intestinal wound healing by promoting enterocyte migration and show beneficial effects on newborn rats with NEC.
authors: 1] Department of General Surgery, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, P. R. China [2] Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors: Qingfeng
authors: Q
authors: Sheng
authors: Department of General Surgery, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, P. R. China.
authors: Zhibao
authors: Z
authors: Lv
authors: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors: Wei
authors: W
authors: Cai
authors: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors: Huanlei
authors: H
authors: Song
authors: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors: Linxi
authors: L
authors: Qian
authors: Department of General Surgery, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, P. R. China.
authors: Huaibo
authors: H
authors: Mu
authors: Department of General Surgery, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, P. R. China.
authors: Jingyi
authors: J
authors: Shi
authors: Department of Pathology, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, P. R. China.
authors: Xueli
authors: X
authors: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D018938:Caco-2 Cells; D002465:Cell Movement / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D054399:Receptors, CCR6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D014945:Wound Healing / Q000187:drug effects*; D023083:beta-Defensins / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D057134:Antibodies, Neutralizing; C106311:CCR6 protein, human; C422950:DEFB103A protein, human; D018836:Inflammation Mediators; D018994:Myosin Light Chains; D054399:Receptors, CCR6; D023083:beta-Defensins; C066737:RHOA protein, human; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein