Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice.
BACKGROUND
Fat tissue is a common material for autologous transplantation in plastic and reconstructive surgery. Basic fibroblast growth factor (bFGF) ameliorates the fat graft survival. A transplantation model has shown the gene expression of matrix metalloproteinases (MMPs) to increase in adipocytes. The aim of this study is to investigate the role of MMPs in the amelioration of survival by bFGF.


METHODS
3T3-L1 adipocytes were incubated with or without 10 microg mL(-1) bFGF for 8 h in the presence or absence of the MMP inhibitor GM6001, vascular endothelial growth factor (VEGF), MMP-2 or anti-bFGF antibody to study the effect of bFGF on MMP-2 mRNA expression, MMP-2 activity, fat accumulation or 2-deoxyglucose uptake. Collagen sheets containing l x l0(7) adipocytes with or without bFGF in the presence or absence of GM6001 were subcutaneously transplanted into mice, and the appearance, histology, mRNA expression and fat accumulation of the grafts were analysed 4 weeks after transplantation.


RESULTS
The MMP-2 expression was drastically induced by bFGF among MMPs in 3T3-L1 adipocytes. MMP-2 accelerated fat accumulation, peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNA expression, and glucose uptake to an extent similar to those induced by bFGF, respectively. The bFGF-induced increases were inhibited by the blocking of MMP-2. The transplantation of adipocytes into mice showed that bFGF ameliorates the appearance and fat accumulation, as well as mRNA expression in grafts. These effects were almost or partly inhibited by a MMP blockade.


CONCLUSIONS
MMP-2 may be involved in the mechanism by which bFGF ameliorates the survival of fat grafts.
Department of Plastic and Reconstructive Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
D
D
Kuramochi
H
H
Unoki
H
H
Bujo
Y
Y
Kubota
M
M
Jiang
N
N
Rikihisa
A
A
Udagawa
S
S
Yoshimoto
M
M
Ichinose
Y
Y
Saito
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000637:transplantation*; D000818:Animals; D002470:Cell Survival; D004151:Dipeptides / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D004151:Dipeptides; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D047495:PPAR gamma; D011480:Protease Inhibitors; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D020778:Matrix Metalloproteinase 2; D005947:Glucose