Increase in size and number of bronchial
blood vessels as well as hyperaemia are factors that contribute to
airway wall remodelling in
patients with chronic
airway diseases, such as
asthma and
chronic obstructive pulmonary diseases (
COPD). Expression of
transforming growth factor 1 (TGF-1), a multifunctional
cytokine as well as
vascular endothelial growth factor (
VEGF), a key angiogenic molecule, has been shown in the inflammed airways in
patients with chronic
airway diseases. TGF-1 has been implicated in the
regulation of
extracellular matrix, leading to
airway remodelling in
patients with chronic
airway diseases. However, the
role of TGF-1 in regulating
VEGF expression in
patients with chronic
airway diseases, as well as the underlying mechanisms are not yet well established. We investigated whether TGF-1 stimulates
VEGF expression
in vitro and hence could influence vascular remodelling. Cultured
human airway smooth muscle cells (HASMC) were
serum deprived for 60 h before incubation with 5ng/ml of TGF-1 for different
time points. Control
cells received
serum-free
culture medium. TGF‑1,
treatment resulted in
time dependent HASMC
cell proliferation with maximal values for
DNA biosynthesis at 24 h and
cell number at 48 h.
Northern blot analysis of
VEGF mRNA expression showed increased levels in
cells treated with TGF-1 for 4 to 8 h. TGF-1 also induced a
time-dependent release of
VEGF proteins in the
conditioned medium after 48 h of
treatment. Furthermore, the
ability of HASMC-released
VEGF proteins to induce
human umbilical vein endothelial cells proliferation was inhibited by
VEGF receptor antagonist, confirming that TGF-1 induced
VEGF was biologically active. We conclude that TGF-1 in addition to an
extracellular matrix regulator also could
play a key
role in bronchial
angiogenesis and vascular remodelling via
VEGF pathway in
asthma.