TRANSFORMING GROWTH-FACTOR-BETA-1 STIMULATES TYPE-V COLLAGEN EXPRESSION IN BOVINE VASCULAR SMOOTH-MUSCLE CELLS

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.