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

Mara Pilmane, Linda Ozoliņa, Zane Ābola, Aigars Petersons, Vjačeslavs Popkovs, Anita Dabužinskiene, Janis Vetra

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalMedicina
Volume47
Issue number8
DOIs
Publication statusPublished - 2011

Keywords

  • Atresia
  • Children
  • Esophagus
  • Growth factors
  • Immunohistochemistry

Field of Science

  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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