title: Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat.
abstract: Angiogenesis is important for adult tissue regeneration as well as normal development. Vascular endothelial growth factor (VEGF) is a unique potent angiogenic factor, and plays an essential role in regulating angiogenesis during embryonic development, normal tissue growth, and tissue regeneration. Recent evidence shows that nerve growth factor (NGF) also plays a role as an angiogenic regulator as well as a well-known neurotrophic factor. The aim of this study was to investigate whether thymus regeneration accompanies reparative angiogenesis and also to evaluate whether the thymic expression of VEGF is regulated by NGF in vivo and in vitro. Here, we show that high VEGF mRNA and protein levels are concomitant with reparative angiogenesis that occurs dramatically during regeneration following acute involution induced by cyclophosphamide (CY) in the rat thymus. Fluorescent thymus angiography using FITC-dextran showed that thymic regeneration is associated with a much denser capillary network compared with normal control thymus. Furthermore, the expressions of NGF and TrkA were highly increased during thymic regeneration. We also show that NGF mediates thymic epithelial induction of VEGF expression in vitro and in vivo. Taken together, our results suggest that NGF-mediated VEGF up-regulation in thymic epithelial cells may contribute to reparative angiogenesis during thymic regeneration in adult.
authors.affiliation: Department of Anatomy, School of Medicine, Pusan National University, Busan, 602-739, South Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Kim
authors.forename: Jong-Gab
authors.initials: JG
authors.lastname: Kim
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Bae
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Bae
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Wee
authors.forename: Tae-Woo
authors.initials: TW
authors.lastname: Kim
authors.forename: Bong-Seon
authors.initials: BS
authors.lastname: Kim
authors.forename: Jae-Bong
authors.initials: JB
authors.lastname: Kim
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
authors.forename: Sik
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000792:Angiography; D000818:Animals; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000633:toxicity; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D008297:Male; D018919:Neovascularization, Physiologic; D020932:Nerve Growth Factor / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D012038:Regeneration; D013047:Specific Pathogen-Free Organisms; D013950:Thymus Gland / Q000166:cytology / Q000473:pathology / Q000502:physiology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D011506:Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D003520:Cyclophosphamide; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D016650:Fluorescein-5-isothiocyanate