title: Nerve growth factor is critical requirement for in vitro angiogenesis in gastric endothelial cells.
abstract: Angiogenesis is critical for the healing of gastric mucosal injury and is considered to be primarily regulated by vascular endothelial growth factor (VEGF), the fundamental proangiogenic factor. The role of nerve growth factor (NGF) in gastric angiogenesis is unknown. We examined the expression of NGF and its TrkA receptor in endothelial cells (ECs) isolated from gastric mucosa of rats (GMECs), the effect of NGF treatment on in vitro angiogenesis in GMECs, and, the mechanisms underlying NGF's proangiogenic actions. Isolated GMECs from Fisher rats were treated with vehicle, NGF (10-1,000 ng/ml), VEGF (20 ng/ml), or NGF+VEGF. To determine whether and to what extent NGF is critical for angiogenesis in GMECs, we silenced NGF expression using specific siRNA and examined in vitro angiogenesis with and without treatment with exogenous NGF and/or VEGF. Treatment of GMECs with NGF significantly increased in vitro angiogenesis similar to that seen in GMECs treated with VEGF. Silencing of NGF in GMECs abolished angiogenesis, and this effect was reversed only by exogenous NGF but not VEGF, which indicates a direct proangiogenic action of NGF on GMECs that is, at least in part, distinct and independent of VEGF. NGF's proangiogenic action on GMECs was mediated via PI3-K/Akt signaling. This study showed for the first time that gastric mucosal ECs express NGF and its receptor TrkA and that NGF is critical for angiogenesis in these cells.
authors.affiliation: Medical and Research Services, Veterans Affairs Long Beach Healthcare System, Long Beach, California, and the Department of Medicine, University of California, Irvine, California; and.
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
authors.affiliation: Medical and Research Services, Veterans Affairs Long Beach Healthcare System, Long Beach, California, and the Department of Medicine, University of California, Irvine, California; and.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Jones
authors.affiliation: Jagiellonian University Medical School, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.affiliation: Medical and Research Services, Veterans Affairs Long Beach Healthcare System, Long Beach, California, and the Department of Medicine, University of California, Irvine, California; and atarnawski@yahoo.com.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Tarnawski
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D020917:Receptor, trkA; D051057:Proto-Oncogene Proteins c-akt
keywords: PI3-K/Akt; angiogenesis; endothelial cells; nerve growth factor