Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat.
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.
Park
Hyun-Joo
HJ
Department of Anatomy, School of Medicine, Pusan National University, Busan, 602-739, South Korea.
Kim
Mi Na
MN
Kim
Jong-Gab
JG
Bae
Yun-Hee
YH
Bae
Moon-Kyoung
MK
Wee
Hee-Jun
HJ
Kim
Tae-Woo
TW
Kim
Bong-Seon
BS
Kim
Jae-Bong
JB
Bae
Soo-Kyung
SK
Yoon
Sik
S
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*
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