Roles of angiogenic factors and endothelin-1 in gastric XXXX .

@entity5 @entity1066 @entity3621 @entity1534 @entity1412 @entity669 @entity2275
Endothelins (ETs) participate directly and indirectly in angiogenesis via ET receptors. During early fetal angiogenesis, vascular endothelial growth factor (VEGF) and its receptors kinase insert domain-containing receptor (KDR) and fms-like @entity669 kinase-1 (Flt-1) are required for the development of the systemic vasculature. In late angiogenesis, stromal-cell-derived factor (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) act in an organ-specific manner to promote the formation and development of large blood vessels supplying the gastrointestinal tract. We studied the roles of these ligand receptors in angiogenesis during @entity2275 . We studied the following five groups, each consisting of ten cases of endoscopically confirmed gastric @entity1066 : active stage (GA), @entity5 ( @entity1412 ) of @entity2275 located in the angulus; @entity1534 (Hp)-positive @entity3621 (gast+); and Hp-negative @entity3621 (gast-). All cases in the @entity1066 groups were Hp-positive. The study materials consisted of frozen biopsy specimens of lesions arising in the angulus. ET-1 was measured by enzyme immunoassay. The other factors were assayed by reverse-transcription-PCR. The distributions of ET-1, ETA receptor (ETAR), SDF-1 and CXCR4 in the gastric mucosa were evaluated by enzyme immunoassay. ET-1 and ETAR reached peak levels during the GH (ET: P<0.05, ETAR: P<0.01). VEGF mRNA increased slightly during the GA, but did not differ significantly among the groups. KDR and Flt-1 levels were high during the GA, the level being significantly higher than those during the GH and @entity1412 (P<0.05). SDF-1 levels significantly decreased during the GH and @entity1412 compared with levels during the GA, and CXCR4 significantly increased during the GH and @entity1412 (P<0.01). On immunostaining, ET-1-positive cells and ETAR-positive cells were found in the endothelium, vascular smooth muscle and gastric epithelium, and CXCR4-positive cells were found in the endothelium and gastric epithelium during the GH and @entity1412 . Our results suggest that VEGF receptors are mainly expressed early in @entity1066 development and participate in the initial stage of angiogenesis. SDF-1 receptors and ETAR are primarily expressed during the GH and @entity1412 and are involved in vascular maturation and gastric mucosal regeneration during late angiogenesis.
