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. 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.
Lawrence
R
R
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Hartmann
D J
DJ
Sonenshein
G E
GE
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D015152:Blotting, Northern; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000302:isolation & purification; D004247:DNA / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D004247:DNA