Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo - Induction by tumor necrosis factor-alpha and lipopolysaccharide
Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo - Induction by tumor necrosis factor-alpha and lipopolysaccharide
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DOI：
10.1172/jci118404
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发表时间：
1996-01-01
影响因子：
15.9
通讯作者：
Loskutoff, DJ
中科院分区：
文献类型：
--
作者：
Samad, F;Yamamoto, K;Loskutoff, DJ
尽管血浆纤溶酶原激活物抑制剂 1 (PAI-1) 升高与肥胖相关，但对其组织或细胞起源或肥胖条件下导致 PAI-1 水平升高的事件知之甚少。由于啮齿动物在肥胖期间和内毒素治疗后 TNF-α 都会增加，因此我们检查了这些药物对 CB6 小鼠脂肪组织中 PAI-1 基因表达的影响。在未治疗的小鼠中，在成熟脂肪细胞和基质血管细胞中均检测到了 PAI-1 mRNA。 TNF-α和内毒素均显着增加脂肪组织中的PAI-1 mRNA，在3-8小时达到峰值。对未处理小鼠的脂肪组织进行原位杂交分析显示，仅在血管壁内的平滑肌细胞中存在微弱的 PAI-1 mRNA 信号，相反，在内毒素或 TNF-α 处理后，在脂肪细胞和血管外膜细胞中也检测到了 PAI-1 mRNA。内毒素还诱导内皮细胞中的 PAI-1，而 TNF-α。另外在平滑肌细胞中诱导它。培养中的成熟3T3-L1脂肪细胞也表达PAI-1 mRNA，并且其合成率也被TNF-α上调。这些研究表明，脂肪组织本身可能是肥胖条件下血浆中 PAI-1 水平升高的一个重要因素。
Although elevated plasma plasminogen activator inhibitor 1 (PAI-1) is associated with obesity, very little is known about its tissue or cellular origin, or about the events that lead to increased PAI-1 levels under obese conditions. Since TNF-alpha is increased in rodents both during obesity and in response to endotoxin treatment, we examined the effects of these agents on PAI-1 gene expression in the adipose tissue of CB6 mice, In untreated mice, PAI-1 mRNA was detected in both mature adipocytes and in stromal vascular cells. Both TNF-alpha and endotoxin significantly increased PAI-1 mRNA in the adipose tissue, peaking at 3-8 h. In situ hybridization analysis of adipose tissue from untreated mice revealed a weak signal for PAI-1 mRNA only in the smooth muscle cells within the vascular wall, In contrast, after endotoxin or TNF-alpha treatment, PAI-1 mRNA also was detected in adipocytes and in adventitial cells of vessels. Endotoxin also induced PAI-1 in endothelial cells, while TNF-alpha. additionally induced it in smooth muscle cells. Mature 3T3-L1 adipocytes in culture also expressed PAI-1 mRNA, and its rate of synthesis was also upregulated by TNF-alpha. These studies suggest that the adipose tissue itself may be an important contributor to the elevated PAI-1 levels observed in the plasma under obese conditions.