title: Growth factors, their receptors, neuropeptide-containing innervation, and matrix metalloproteinases in the proximal and distal ends of the esophagus in children with esophageal atresia.
abstract: OBJECTIVE
  The pathogenesis of esophageal atresia (EA) remains unknown despite a relatively high incidence of this anomaly in population affecting 1 newborn per 3000 live births. The aim of this study was to examine the relative occurrence of growth factors, their receptors, neuropeptide-containing innervation, and tissue-degradating enzymes--matrix metalloproteinases--in the proximal and distal parts of the esophagus with EA.
  
  
  METHODS
  A histopathological study was conducted on 15 patients with EA. Tissues were processed for NGFRp75, PGP 9.5, TGF-β, FGFR, VEGF, EGFR and MMP-2 by means of biotin-streptavidin immunohistochemistry.
  
  
  RESULTS
  In the control and EA-affected distal esophageal specimens, numerous and abundant NGFR-containing structures were detected, while in the proximal part of the esophagus, a decrease in their number was observed in patients. PGP 9.5 also marked neuronal structures similarly. TGF-β was found only in occasional cells in the EA-affected esophageal specimens, while control material demonstrated moderate to numerous TGF-β-containing structures. Abundance of FGFR and only occasional appearance of VEGF-positive cells were found in both the control and EA-affected material. A moderate number of connective tissue cells in controls contained EGFR. Compared with controls, the number of MMP-2 expressing cells in the EA-affected tissues was decreased in the proximal esophagus.
  
  
  CONCLUSIONS
  A decrease in PGP 9.5-containing neuronal structures in the proximal esophagus supports insufficient innervation of this part of the organ in EA. A decrease in MMP-2 positive cells in the esophageal atresia-affected proximal esophagus indicates also a possible decrease of tissue adaptive and regenerative reactions. Low expression of TGF-β and almost the absence of EGFR in the EA-affected specimens may result in disturbances of cell growth, proliferation, and differentiation, indicating a significant role of these substances in morphopathogenesis of EA. FGFR and VEGF seem not to characterize EA pathogenesis.
authors: Institute of Anatomy and Anthropology, Riga Stradins University, Dzirciema str. 16, 1007 Riga, Latvia. pilmane@latnet.lv
authors: Māra
authors: M
authors: Pilmane
authors: Linda
authors: L
authors: Ozoliņa
authors: Zane
authors: Z
authors: Ābola
authors: Aigars
authors: A
authors: Pētersons
authors: Vjačeslavs
authors: V
authors: Popkovs
authors: Anita
authors: A
authors: Dabužinskienė
authors: Jānis
authors: J
authors: Vētra
mesh_terms: D002648:Child; D066246:ErbB Receptors / Q000378:metabolism; D004933:Esophageal Atresia / Q000378:metabolism*; D004947:Esophagus / Q000002:abnormalities* / Q000294:innervation / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides; D020800:Receptor, Nerve Growth Factor; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; C482860:UCHL1 protein, human; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors; D051496:Receptor, Fibroblast Growth Factor, Type 1; D043222:Ubiquitin Thiolesterase; D020778:Matrix Metalloproteinase 2