Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo.
Nerve growth factor (NGF) has important functions during embryonic development and on various tissues and organs under normal and pathological conditions during the extrauterine life. RT-PCR analysis and immunological methods demonstrate that human umbilical vein endothelial cells (HUVECs) express the NGF receptors trkA(NGFR) and p75NTR. NGF treatment caused a rapid phosphorylation of trkA(NGFR) in HUVECs, determining a parallel increase of phosphorylated ERK1/2. Accordingly, NGF induced a significant increase in HUVEC proliferation that was abolished by the trkA(NGFR) inhibitor K252a. Also, HUVECs express significant levels of NGF under standard culture conditions that were up-regulated during serum starvation. Endogenous NGF was responsible for the basal levels of trkA(NGFR) and ERK1/2 phosphorylation observed in untreated HUVEC cultures. Finally, NGF exerted a potent, direct, angiogenic activity in vivo when delivered onto the chorioallantoic membrane of the chicken embryo. The data indicate that NGF may play an important role in blood vessel formation in the nervous system and in several pathological processes, including tumors and inflammatory diseases. Unraveling mechanisms of NGF-dependent angiogenesis could provide valuable tools for novel therapeutic approaches in antiangiogenic therapy.
Cantarella
Giuseppina
G
Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, I-95125 Catania, Italy.
Lempereur
Laurence
L
Presta
Marco
M
Ribatti
Domenico
D
Lombardo
Gabriella
G
Lazarovici
Philip
P
Zappalà
Giovanna
G
Pafumi
Carlo
C
Bernardini
Renato
R
D000818:Animals; D019898:Autocrine Communication; D001808:Blood Vessels / Q000033:anatomy & histology / Q000196:embryology; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000033:anatomy & histology / Q000098:blood supply / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D020932:Nerve Growth Factor / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA