Collagen synthesis of human arterial smooth muscle cells: effects of platelet-derived growth factor, transforming growth factor-beta 1 and interleukin-1.
The effects of platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-beta 1) 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 dodecylsulfate-polyacrylamide 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-beta 1 (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 IV collagen and increased that of type V collagen. TGF-beta 1 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-beta 1 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.
Department of Pathology, School of Medicine, Kanazawa University, Japan.
Y
Y
Okada
S
S
Katsuda
H
H
Watanabe
I
I
Nakanishi
D000328:Adult; D001011:Aorta; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000187:drug effects; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D003094:Collagen; D004247:DNA