Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice

Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice
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DOI:
10.1111/j.1365-2362.2008.02023.x
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发表时间:
2008-10-01
影响因子:
5.5
通讯作者:
Saito, Y.
Saito, Y.
中科院分区:
医学3区
文献类型:
--
作者:
Kuramochi, D.;Unoki, H.;Saito, Y.

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背景脂肪组织是整形和重建手术中自体移植的常用材料。碱性成纤维细胞生长因子(bFGF)可改善脂肪移植物的存活率。移植模型显示脂肪细胞中基质金属蛋白酶(MMPs)的基因表达增加。本研究的目的是探讨MMPs在bFGF改善生存中的作用。材料与方法3T3-L1脂肪细胞在MMP抑制剂GM6001、血管内皮生长因子(VEGF)、MMP-2或抗bFGF抗体存在或不存在的情况下,加入或不加入10 μ g mL(-1) bFGF孵育8小时,研究bFGF对MMP-2 mRNA表达、MMP-2活性、脂肪积累或2-去氧葡萄糖摄取的影响。将含有1 × 10(7)个脂肪细胞(含或不含bFGF, GM6001存在或不存在)的胶原片皮下移植到小鼠体内,并在移植4周后分析移植物的外观、组织学、mRNA表达和脂肪堆积情况。结果bFGF可显著诱导3T3-L1脂肪细胞中MMP-2的表达。MMP-2分别加速脂肪积累、过氧化物酶体增殖物激活受体γ (PPAR γ) mRNA表达和葡萄糖摄取,其程度与bFGF诱导的相似。阻断MMP-2可抑制bfgf诱导的升高。脂肪细胞移植小鼠的实验表明,bFGF改善了移植物的外观和脂肪堆积,并改善了移植物mRNA的表达。MMP阻断几乎或部分抑制了这些作用。结论MMP-2可能参与bFGF改善脂肪移植物存活的机制。
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 mu g 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.