Expression of Tie-2 and angiopoietin-1 and -2 in early phase of ulcer healing

J Gastroenterol. 2003;38(5):431-5. doi: 10.1007/s00535-002-1078-3.

Abstract

Background: Angiogenesis is an important process in tissue development and wound healing. The Tie-2 receptor tyrosine kinases and ligands, angiopoietin (Ang)-1 and -2 have been postulated to play key roles in vascular development. The purpose of this study was to evaluate the expression of Tie-2 and Ang-1 and -2 in an acetic acid-induced gastric ulcer healing process in rats.

Methods: Gastric specimens were obtained at 0 (control), 1, 3, 5, 7, and 14 days after ulcer induction for reverse transcription polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical analysis.

Results: Expression of Tie-2 and Ang-1 and -2 mRNAs was detected in normal gastric tissue and ulcerative tissues by RT-PCR. Western blot analysis revealed that Tie-2 expression reached a maximum on the third to fifth days. Expression of Ang-1 and -2 peaked on the first day. Ang-1 expression gradually became weaker in 2 weeks, whereas Ang-2 expression returned to normal in a few days. Immunohistochemically, Tie-2 was expressed constitutively in the endothelial cells of pre-existing vessels of the gastric wall, and Tie-2 expression was increased in the new capillaries of the ulcer base.

Conclusions: These findings suggest that Tie-2 and Ang-1 and -2 play an important role in angiogenesis in the early phase of ulcer healing.

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Angiopoietin-1
  • Angiopoietin-2
  • Animals
  • Blotting, Western
  • Immunohistochemistry
  • Male
  • Membrane Glycoproteins / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, TIE-2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wound Healing / physiology*

Substances

  • Angiogenesis Inducing Agents
  • Angiopoietin-1
  • Angiopoietin-2
  • Angpt1 protein, rat
  • Membrane Glycoproteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-2