Wdnm1-like, a new adipokine with a role in MMP-2 activation.
Wdnm1-like, a new adipokine with a role in MMP-2 activation.
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DOI：
10.1152/ajpendo.90316.2008
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发表时间：
2008-05
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影响因子：
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通讯作者：
Yu Wu;C. Smas
中科院分区：
文献类型：
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作者：
Yu Wu;C. Smas
白色脂肪组织的功能是储存能量和作为内分泌器官。DNA微阵列分析使我们确定Wdnm 1-like，乳清酸性蛋白/四-二硫键核心（WAP/4-DSC）家族的远缘成员，作为白色和棕色脂肪形成的分化依赖性基因。Wdnm 1样是一种新的6.8 kDa的蛋白质，蛋白质印迹分析显示分泌到培养基中。Wdnm 1样转录物选择性地在脂肪组织和肝脏中表达，并且在白色脂肪贮库中比在棕色脂肪贮库中富集约500倍。WAT的细胞分级显示Wdnm 1样转录物表达仅限于脂肪细胞群。在3 T3-L1前脂肪细胞（一种白色脂肪形成的体外模型）中的研究表明，Wdnm 1样转录物在脂肪形成诱导的6小时内增加，到第7天增加约17，000倍。Wdnm 1样蛋白的显著上调也伴随ScAP-23前脂肪细胞和原代前脂肪细胞的白色脂肪形成。3 T3-L1脂肪细胞的TNF-α处理使Wdnm 1样转录水平增加2.4倍，并且通过用p38 MAP激酶抑制剂SB 203580预处理而减弱。许多WAP/4-DSC家族蛋白质作为蛋白酶抑制剂起作用。这与细胞外重塑在脂肪形成中的作用一起，使我们解决了Wdnm 1样对基质金属蛋白酶（MMP）活性的影响。明胶酶谱的HT 1080纤维肉瘤细胞转染Wdnm 1样表达结构显示活性MMP-2的水平显着增加。我们的研究结果确定了一个新成员的脂肪细胞“分泌”的功能，以提高MMP-2的活性。我们推测Wdnm 1样可能在脂肪形成的细胞外环境重塑中发挥作用，以及在脂肪细胞是关键基质成分的肿瘤微环境中发挥作用。
White adipose tissue functions in energy storage and as an endocrine organ. DNA microarray analysis led us to identify Wdnm1-like, a distant member of the whey acidic protein/four-disulfide core (WAP/4-DSC) family, as a differentiation-dependent gene in white and brown adipogenesis. Wdnm1-like is a novel 6.8-kDa protein, and Western blot analysis reveals secretion into culture media. Wdnm1-like transcript is selectively expressed in adipose tissue and liver and is enriched approximately 500-fold in white adipose depots vs. brown. Cellular fractionation of WAT demonstrates Wdnm1-like transcript expression is restricted to the adipocyte population. Studies in 3T3-L1 preadipocytes, an in vitro model of white adipogenesis, indicate Wdnm1-like transcript increases within 6 h of adipogenic induction with an approximately 17,000-fold increase by day 7. Dramatic upregulation of Wdnm1-like also accompanies white adipogenesis of ScAP-23 preadipocytes and primary preadipocytes. TNF-alpha treatment of 3T3-L1 adipocytes increased Wdnm1-like transcript level 2.4-fold and was attenuated by pretreatment with the p38 MAP kinase inhibitor SB203580. A number of WAP/4-DSC family proteins function as protease inhibitors. This, taken with the role of extracellular remodeling in adipogenesis, led us to address effects of Wdnm1-like on matrix metalloproteinase (MMP) activity. Gelatin zymography of HT1080 fibrosarcoma cells transfected with a Wdnm1-like expression construct revealed markedly increased levels of active MMP-2. Our findings identify a new member of the adipocyte "secretome" that functions to enhance MMP-2 activity. We postulate that Wdnm1-like may play roles in remodeling of the extracellular milieu in adipogenesis, as well as in tumor microenvironments where adipocytes are key stromal components.