Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity
Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity
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DOI：
10.2337/diabetes.51.4.1093
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Lijnen, HR
中科院分区：
文献类型：
--
作者：
Maquoi, E;Munaut, C;Lijnen, HR
在营养性肥胖小鼠模型中，研究了基质金属蛋白酶（MMP）系统在脂肪组织病理生理中的潜在作用。采用半定量RT-PCR方法，在标准或高脂饮食15周的小鼠脂肪组织中，检测16种MMPs和4种MMPs组织抑制剂（TIMTs）的mRNA水平。在标准饮食的小鼠中，除MMP-8外，所有的AIMP和TIMP转录本都在性腺和皮下库中检测到。在肥胖小鼠中，MMP-3、-11、-12、-13、-14和TIMP-1 mrna表达上调，而MMP-7、-9、-16、-24和TIMP-4 mrna表达下调。大多数MMP和TIMP mrna在间质血管细胞中的表达水平高于成熟脂肪细胞。通过原位荧光酶谱分析脂肪组织发现了mmp依赖的蛋白水解活性，表明在完整组织中存在活性的MMPs。体外将成脂细胞3T3-F442A转化为成熟脂肪细胞与MMP和TIMP表达的大量调节有关。此外，这种体外脂肪生成在合成的MMP抑制剂的存在下减少。因此，脂肪组织表达大量调节脂肪细胞分化的MMPs和TIMPs。
The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and 4 tissue inhibitors of MMPs (TIMTs) were measured by semiquantitative RT-PCR in adipose tissue isolated from mice maintained for 15 weeks on a standard or high-fat diet. In mice on standard diet, with the exception of MMP-8, all AIMP and TIMP transcripts were detected in both gonadal and subcutaneous depots. In obese mice, the expression of MMP-3, -11, -12, -13, and -14 and TIMP-1 mRNAs was upregulated, whereas that of MMP-7, -9, -16, and -24 and TIMP-4 was downregulated. Most MMP and TIMP mRNAs were expressed at higher levels in stromal-vascular cells than in mature adipocytes. Analysis of adipose tissue by in situ fluorescent zymography revealed MMP-dependent proteolytic activities, demonstrating the presence of active MMPs in the intact tissue. In vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes was associated with substantial modulations of MMP and TIMP expression. Moreover, this in vitro adipogenesis was reduced in the presence of a synthetic MMP inhibitor. Thus, the adipose tissue expresses a large array of MMPs and TIMPs, which modulate adipocyte differentiation.