Growth factors, their receptors, neuropeptide-containing innervation, and matrix metalloproteinases in the proximal and distal ends of the esophagus in children with esophageal atresia

Medicina (Kaunas). 2011;47(8):453-60. Epub 2011 Nov 18.

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.

Materials and 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.

MeSH terms

  • Child
  • ErbB Receptors / metabolism
  • Esophageal Atresia / metabolism*
  • Esophagus / abnormalities*
  • Esophagus / innervation
  • Esophagus / metabolism*
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Matrix Metalloproteinase 2 / metabolism
  • Nerve Fibers / metabolism
  • Neurons / metabolism*
  • Neuropeptides / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, Nerve Growth Factor / metabolism
  • Receptors, Growth Factor / metabolism*
  • Transforming Growth Factor beta / metabolism
  • Ubiquitin Thiolesterase / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • Neuropeptides
  • Receptor, Nerve Growth Factor
  • Receptors, Growth Factor
  • Transforming Growth Factor beta
  • UCHL1 protein, human
  • Vascular Endothelial Growth Factor A
  • EGFR protein, human
  • ErbB Receptors
  • Receptor, Fibroblast Growth Factor, Type 1
  • Ubiquitin Thiolesterase
  • Matrix Metalloproteinase 2