Differences in the biological activities of transforming growth factor-beta and platelet-derived growth factor in vivo.
Transforming growth factor-beta 1 (TGF-beta 1 and recombinant platelet-derived growth factor-BB (rPDGF-BB) promoted an extensive, dose-dependent development of fibrous connective tissue when continuously delivered for 8 days by mini-osmotic pumps implanted subcutaneously in adult guinea pigs. Biochemical analyses demonstrated that TGF-beta 1 and rPDGF-BB stimulated dose-dependent increases in the dry weight, and protein, DNA, collagen, and glycosaminoglycan (GAG) contents of the fibrous connective tissue capsule that enveloped the pumps. The GAG/DNA mass ratio was markedly elevated by TGF-beta 1, but the collagen/DNA, protein/DNA, and collagen/protein ratios were not significantly increased. In contrast, rPDGF-BB generally decreased these mass ratios. Histological analyses suggested that this was due to the fact that rPDGF-BB induced a very cellular response with a marked influx of neutrophils and fibroblasts. TGF-beta 1 induced significantly less cellular response, which consisted primarily fibroblasts and macrophages. These results indicated that rPDGF-BB and TGF-beta 1 induced connective tissue deposition in vivo in a dose-dependent fashion, although the cellular nature of the responses as well as the structural composition of the extracellular matrices were clearly distinguishable between the two growth factors.
Ogawa
Y
Y
Celtrix Laboratories, Palo Alto, CA 94303.
Ksander
G A
GA
Pratt
B M
BM
Sawamura
S J
SJ
Ziman
J M
JM
Gerhardt
C O
CO
Avis
P D
PD
Murray
M J
MJ
McPherson
J M
JM
D000818:Animals; D003238:Connective Tissue / Q000378:metabolism; D003239:Connective Tissue Cells; D006025:Glycosaminoglycans / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D006025:Glycosaminoglycans; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta