Collagen synthesis of human arterial smooth muscle cells: effects of platelet-derived growth factor, transforming growth factor-beta 1 and interleukin-1.

Abstract

The effects of platelet‐derived growth factor (PDGF), transforming growth factor‐β1 (TGF‐β1) and interleukin‐1 (IL‐1) on collagen synthesis of cultured human arterial smooth muscle cells in a confluent state were investigated. Synthetic activity of collagenous protein was determined with [3H]‐proline uptake, and subsequent analysis of collagen types by sodium dodecylsulfte‐polyacrylmide gel electrophoresis (SDS‐PAGE) followed by fluorography. Although PDGF (0.5 U/mL and 5.0 U/mL) enhanced total collagen synthesis per dish, it suppressed total collagen synthesis per DNA (DNA content in a dish). TGF‐β1 (10 pmol/L and 100 pmol/L) enhanced total collagen synthesis both per dish and per DNA. IL‐1 (0.1 U/mL and 1.0 U/mL) suppressed total collagen synthesis both per dish and per DNA. A fluorogram revealed that human arterial smooth muscle cells synthesize types I, III, IV and V collagen. Densitometric analysis showed PDGF suppressed the proportion of type V collagen. TGF‐β1 increased the proportions of types IV and V collagen. IL‐1 elicited un‐remarkable change in the proportion of collagen types. These results suggest that, in the event of human atherosclerosis, TGS‐β1 is most effective in enhancing collagen synthesis, and PDGF modulates collagen metabolism by stimulating a cell division of smooth muscle cells with a resultant increase of collagenous protein, especially of type V collagen.