The bioactivity of transforming growth factor-beta1 can be regulated via binding to dermal collagens in mink lung epithelial cells.
BACKGROUND
The bioactivity of transforming growth factor-beta1 (TGF-beta1) is known to be regulated by some components of the extracellular matrix (ECM), but the possibility that it might be regulated by collagen, the richest ECM component, has never been previously reported.


OBJECTIVE
This study was designed to investigate the possible role that different types of collagens might play on the bioactivity of TGF-beta1.


METHODS
The interaction of 125I-TGF-beta1 and various types of collagen was examined by a solid-phase assay and by a co-precipitation assay. The bioactivity of TGF-beta1 was assessed by a proliferation assay in which mink lung epithelial cells were examined in the presence and absence of collagens.


RESULTS
Activated native dimeric TGF-beta1 bound to type I collagen in a dose-dependent manner, while monomeric TGF-beta1 bound poorly to the collagen. Type III collagen, and type I gelatin, a heat-denatured type I collagen, also showed a similar interaction with TGF-beta1, however, type IV collagen showed a weak interaction. In the presence of types I and III collagens, the inhibitory effect of TGF-beta1 on the proliferation of mink lung epithelial cells was sustained, thus suggesting that the bioactivity of TGF-beta1 had been enhanced. Type I gelatin also enhanced the inhibition of cell growth, but its effect was weak in comparison with that of type I collagen. The amount of TGF-beta1 which remained intact in the conditioned medium after incubation with MLEC in the presence of types I and III collagens was more than that incubated without collagen.


CONCLUSIONS
Our results suggest that types I and III collagens, the two most abundant components of the interstitial collagens, can potentially bind to activated TGF-beta1 and regulate the bioactivity of this growth factor, thereby possibly maintaining the biologically available TGF-beta1 level.
Shibuya
Hiromi
H
Plastic Surgery, Department of Anatomy, Biology and Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, 879-5593 Oita, Japan.
Okamoto
Osamu
O
Fujiwara
Sakuhei
S
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D008168:Lung / Q000166:cytology*; D008907:Mink; D011485:Protein Binding; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen