COLLAGEN-SYNTHESIS OF HUMAN ARTERIAL SMOOTH-MUSCLE CELLS - EFFECTS OFPLATELET-DERIVED GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-BETA-1 ANDINTERLEUKIN-1

The effects of platelet-derived growth factor (PDGF), transforming gro wth factor-beta1 (TGF-beta1) and interleukin-1 (IL-1) on collagen synt hesis of cultured human arterial smooth muscle cells in a confluent st ate were investigated. Synthetic activity of collagenous protein was d etermined with [H-3]-proline uptake, and subsequent analysis of collag en types by sodium dodecylsulfate-polyacrylmide gel electrophoresis (S DS-PAGE) followed by fluorography. Although PDGF (0.5 U/mL and 5.0 U/m L) enhanced total collagen synthesis per dish, it suppressed total col lagen synthesis per DNA (DNA content in a dish). TGF-beta1 (10 pmol/L and 100 pmol/L) enhanced total collagen synthesis both per dish and pe r DNA. IL-1 (0.1 U/mL and 1.0 U/mL) suppressed total collagen synthesi s both per dish and per DNA. A fluorogram revealed that human arterial smooth muscle cells synthesize types I, III, IV and V collagen. Densi tometric analysis showed PDGF suppressed the proportion of type IV col lagen and increased that of type V collagen. TGF-beta1 increased the p roportions of types IV and V collagen. IL-1 elicited un- remarkable ch ange in the proportion of collagen types. These results suggest that, in the event of human atherosclerosis, TGS-beta1 is most effective in enhancing collagen synthesis, and PDGF modulates collagen metabolism b y stimulating a cell division of smooth muscle cells with a resultant increase of collagenous protein, especially of type V collagen.