Characterization of the long pentraxin PTX3 as a TNFα-induced secreted protein of adipose cells

Characterization of the long pentraxin PTX3 as a TNFα-induced secreted protein of adipose cells
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DOI:
10.1194/jlr.m200382-jlr200
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发表时间:
2003-05-01
影响因子:
6.5
通讯作者:
Amri, EZ
Amri, EZ
中科院分区:
生物学2区
文献类型:
--
作者:
Abderrahim-Ferkoune, A;Bezy, O;Amri, EZ

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前脂肪细胞暴露于长链脂肪酸中可诱导几种脂肪细胞分化标志物的表达。为了在前脂肪细胞中鉴定受脂肪酸调节的新基因和蛋白,我们进行了减法杂交筛选,并鉴定了penttraxin家族的一种蛋白PTX3。PTX3 mRNA的表达在克隆细胞系的脂肪细胞分化过程中是短暂的,在完全分化的细胞中不存在。前脂肪细胞稳定过表达PTX3对脂肪细胞分化无影响。与此相一致,PTX3 mRNA在脂肪组织的基质血管部分表达,而在脂肪细胞部分不表达;然而,在3T3-F442A脂肪细胞中,PTX3基因可以被肿瘤坏死因子α (TNFalpha)以剂量依赖的方式重新诱导。这种作用伴随着3T3-F442A脂肪细胞和小鼠脂肪组织外植体分泌PTX3蛋白。发现遗传性肥胖小鼠的脂肪组织中PTX3 mRNA水平高于对照小鼠,这与它们增加的TNFalpha水平一致。总之,PTX3是一种tnfalpha诱导的蛋白,在慢性低水平炎症状态和肥胖之间提供了新的联系。
Exposure of preadipocytes to long-chain fatty acids induces the expression of several markers of adipocyte differentiation. In an attempt to identify novel genes and proteins that are regulated by fatty acids in preadipocytes, we performed a substractive hybridization screening and identified PTX3, a protein of the pentraxin family. PTX3 mRNA expression is transient during adipocyte differentiation of clonal cell lines and is absent in fully differentiated cells. Stable overexpression of PTX3 in preadipocytes has no effect on adipocyte differentiation. In line with this, PTX3 mRNA is expressed in the stromal-vascular fraction of adipose tissue, but not in the adipocyte fraction; however, in 3T3-F442A adipocytes, the PTX3 gene can be reinduced by tumor necrosis factor alpha (TNFalpha) in a dose-dependent manner. This effect is accompanied by PTX3 protein secretion from both 3T3-F442A adipocytes and explants of mouse adipose tissue. PTX3 mRNA levels are found to be higher in adipose tissue of genetically obese mice versus control mice, consistent with their increased TNFalpha levels. In conclusion, PTX3 appears as a TNFalpha-induced protein that provides a new link between chronic low-level inflammatory state and obesity.