Dermatopontin interacts with transforming growth factor beta and enhances its biological activity.
Dermatopontin, a recently found low-molecular-mass component of the extracellular matrix, was studied for its interaction with decorin and transforming growth factor beta (TGF-beta) and its influence on TGF-beta bioactivity. Dermatopontin reacted with decorin with an apparent Kd of 100 nM in a solid-phase assay. Dermatopontin inhibited the formation of the decorin-TGF-beta1 complex. Decorin also competed with dermatopontin for the binding of this cytokine. The dermatopontin-decorin complex bound 3-fold more TGF-beta1 than did each component individually, and binding was inhibited more strongly by decorin preincubated with dermatopontin than by dermatopontin or decorin alone. Dermatopontin augmented the biological activity of TGF-beta1, as analysed by the expression of luciferase in mink lung epithelial cells transfected with a plasminogen activator inhibitor-promoter-luciferase construct, although dermatopontin itself did not show apparent induction of luciferase. Dermatopontin showed weak inhibitory activity on the proliferation of mink lung epithelial cells, and it enhanced the growth-inhibitory activity of TGF-beta on these cells. Thus dermatopontin increases the cellular response to TGF-beta. These findings strongly suggest that dermatopontin modifies the behaviour of TGF-beta through interaction with decorin in the microenvironment of the extracellular matrix in vivo.
Okamoto
O
O
Department of Dermatology, Oita Medical University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5503, Japan. ookamoto@oita-med.ac.jp
Fujiwara
S
S
Abe
M
M
Sato
Y
Y
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans; D058575:Decorin; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008907:Mink; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; C082019:DPT protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta