title: Radio-sensitivities and angiogenic signaling pathways of irradiated normal endothelial cells derived from diverse human organs.
abstract: The purpose of the present investigation was to study the effects of ionizing radiation on endothelial cells derived from diverse normal tissues. We first compared the effects of radiation on clonogenic survival and tube formation of endothelial cells, and then investigated the molecular signaling pathways involved in endothelial cell survival and angiogenesis. Among the different endothelial cells studied, human hepatic sinusoidal endothelial cells (HHSECs) were the most radio-resistant and human dermal microvascular endothelial cells were the most radio-sensitive. The radio-resistance of HHSECs was related to adenosine monophosphate-activated protein kinase and p38 mitogen-activated protein kinase-mediated expression of MMP-2 and VEGFR-2, whereas the increased radio-sensitivity of HDMECs was related to extracellular signal-regulated kinase-mediated generation of angiostatin. These observations demonstrate that there are distinct differences in the radiation responses of normal endothelial cells obtained from diverse organs, which may provide important clues for protection of normal tissue from radiation exposure.
authors: Department of Microbiology, Center for Advanced Medical Education by BK21 Project, College of Medicine, Inha University, Jungsuck B/D B-Dong 3F, Shinheung-Dong, Jung-Gu, Incheon, Republic of Korea.
authors: Moon-Taek
authors: MT
authors: Park
authors: Eun-Taex
authors: ET
authors: Oh
authors: Min-Jeong
authors: MJ
authors: Song
authors: Hyemi
authors: H
authors: Lee
authors: Heon Joo
authors: HJ
authors: Park
mesh_terms: D043168:Angiostatins / Q000096:biosynthesis / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D002470:Cell Survival / Q000528:radiation effects; D003094:Collagen / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D042783:Endothelial Cells / Q000528:radiation effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000737:chemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D008833:Microcirculation / Q000528:radiation effects; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000737:chemistry; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000528:radiation effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D043168:Angiostatins; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2