RESUMO
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. MATERIALS AND 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.
Assuntos
Adipócitos/metabolismo , Adipócitos/transplante , Metaloproteinase 2 da Matriz/metabolismo , Células 3T3-L1 , Animais , Sobrevivência Celular , Dipeptídeos/farmacologia , Eletroforese em Gel de Poliacrilamida , Fator 2 de Crescimento de Fibroblastos/farmacologia , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo , Inibidores de Proteases/farmacologia , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Fat tissue transplantation is a useful and common clinical technique in the plastic and reconstructive surgeries. To know the nutritional effects on the survival and maintenance of fat grafts, the weights of tissues and cell sizes, and the gene expressions in the fat tissues were analyzed 14 days after transplantation. The body weight and the plasma insulin level in high nutritional group (HNG) were significantly higher (p<0.05) than those in low nutritional group (LNG), respectively. The measurements of cell size showed that there were 32.5% distributed in the diameter less than 2 microm in LNG, significantly higher than 28.5% in HNG. There were 7.5% distributed in the diameter more than 6 microm in LNG, significantly lower than 10.0% in HNG. The mRNA levels of leptin, lipoprotein lipase, and beta(3)-adrenergic receptor were 2.0-, 1.5-, and 1.7-fold higher in HNG than those in LNG, respectively. The levels of hormone sensitive lipase and hexokinase 2 transcripts were not significantly different in both groups. These results show that the systemic nutritional status in host causes the changes of cell size and tissue weight as well as gene expression in the transplanted fat using mice model. The nutritional condition is probably important for the fat graft clinically both as lipid-storage and functional cells.
