Vascular smooth muscle cells (SMCs) produce the bulk of the connective tissue of major arteries, including
collagen types I, III, and V. Recently, we have shown, they also have the capacity to synthesize the alpha 1 chain of type XI, a
collagen related to type V (Brown, K., Lawrence, R., and Sonenshein, G. (1991) J. Biol. Chem. 266, 23268-23273). Furthermore, expression of types V and XI
collagen were coordinately regulated with respect to serum deprivation and cell density in a fashion distinct from that for types I and III. To begin to determine the factors that influence vascular SMC production of types V/XI
collagen, we have examined the effects of
transforming growth factor (
TGF)-beta 1, a major modulator of connective tissue expression. In serum-deprived confluent cultures of bovine pulmonary artery SMCs,
TGF-beta 1 treatment increased the steady-state levels of the mRNAs of
collagen types V and XI, as well as of types I and III,
elastin and
fibronectin. The largest increase was seen for alpha 2(V)
procollagen. The increase in alpha 2(V)
mRNA was detectable by 12 h after addition of 2 ng/ml
TGF-beta 1, and concentrations as little as 0.5 ng/ml were effective. A similar increase in alpha 2(V)
mRNA levels was observed with SMCs derived from the aortic arch and carotid artery.
Type V collagen protein was found to be elevated by
TGF-beta 1 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, [3H]
thymidine incorporation, and steady-state levels of
histone H3.2
mRNA resulted from
TGF-beta 1 treatment. These results suggest that the elevated levels of
TGF-beta 1 in the vessel wall during
atherosclerosis may be, in part, responsible for the increase in
type V collagen that typifies advanced fibrotic lesions.