http://online.liebertpub.com/doi/abs/10.1089/ten.tea.2012.0745
ABSTRACT
Skin
is a major source of secretion of the neurotrophic factors nerve growth
factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3
(NT-3), and glial-derived neurotrophic factor (GDNF) controlling
cutaneous sensory innervation. Beside their neuronal contribution, we
hypothesized that neurotrophic factors also modulate the cutaneous
microvascular network. First, we showed that NGF, BDNF, NT-3, and GDNF
were all expressed in the epidermis, while only NGF and NT-3 were
expressed by cultured fibroblasts, and BDNF by human endothelial cells.
We demonstrated that these peptides are highly potent angiogenic factors
using a human tissue-engineered angiogenesis model. A 40% to 80%
increase in the number of capillary-like tubes was observed after the
addition of 10 ng/mL of NGF, 0.1 ng/mL of BDNF, 15 ng/mL of NT-3, and
50 ng/mL of GDNF. This is the first characterization of the direct
angiogenic effect of NT-3 and GDNF. This angiogenic effect was mediated
directly through binding with the neurotrophic factor receptors
tropomyosin-receptor kinase A (TrkA), TrkB, GFRα-1 and c-ret that were
all expressed by human endothelial cells, while this effect was blocked
by addition of the Trk inhibitor K252a. Thus, if NGF, BDNF, NT-3, and
GDNF may only moderately regulate the microvascular network in normal
skin, they might have the potential to greatly increase angiogenesis in
pathological situations.
No comments:
Post a Comment