R. Lawrence et al., TRANSFORMING GROWTH-FACTOR-BETA-1 STIMULATES TYPE-V COLLAGEN EXPRESSION IN BOVINE VASCULAR SMOOTH-MUSCLE CELLS, The Journal of biological chemistry, 269(13), 1994, pp. 9603-9609
Vascular smooth muscle cells (SMCs) produce the bulk of the connective
tissue of major arteries, including collagen types I, III, and V. Rec
ently, we have shown, they also have the capacity to synthesize the al
pha1 chain of type XI, a collagen related to type V (Brown, K., Lawren
ce, R., and Sonenshein, G. (1991) J. Biol. Chem. 266, 23268-23273). Fu
rthermore, expression of types V and XI collagen were coordinately reg
ulated with respect to serum deprivation and cell density in a fashion
distinct from that for types I and III. To begin to determine the fac
tors that influence vascular SMC production of types V/XI collagen, we
have examined the effects of transforming growth factor (TGF)-beta1,
a major modulator of connective tissue expression. In serum-deprived c
onfluent cultures of bovine pulmonary artery SMCs, TGF-beta1 treatment
increased the steady-state levels of the mRNAs of collagen types V an
d XI, as well as of types I and III, elastin and fibronectin. The larg
est increase was seen for alpha2(V) procollagen. The increase in alpha
2(V) mRNA was detectable by 12 h after addition of 2 ng/ml TGF-beta1,
and concentrations as little as 0.5 ng/ml were effective. A similar in
crease in alpha2(V) mRNA levels was observed with SMCs derived from th
e aortic arch and carotid artery. Type V collagen protein was found to
be elevated by TGF-beta1 treatment in both the conditioned media and
the cell layer associated fraction of pulse-labeled cultures. A slight
decrease in SMC proliferation as judged by DNA content, [H-3]thymidin
e incorporation, and steady-state levels of histone H3.2 mRNA resulted
from TGF-beta1 treatment. These results suggest that the elevated lev
els of TGF-beta1 in the vessel wall during atherosclerosis may be, in
part, responsible for the increase in type V collagen that typifies ad
vanced fibrotic lesions.