Expression of the connexin 43 gene is increased in the kidneys and the lungs of rats injected with bacterial lipopolysaccharide
Expression of the connexin 43 gene is increased in the kidneys and the lungs of rats injected with bacterial lipopolysaccharide
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DOI：
10.1097/00024382-199808000-00003
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发表时间：
1998-08-01
期刊：
影响因子：
3.1
通讯作者：
De Maio, A
中科院分区：
文献类型：
--
作者：
Fernandez-Cobo, M;Gingalewski, C;De Maio, A
在分子水平上，炎症反应的特点是各器官系统基因表达的变化。已观察到炎症期间肝脏中表达发生改变的一种基因是连接蛋白 (Gx) 32。Ox 基因编码包含间隙连接的半通道的多肽亚基。在本研究中，在注射亚致死剂量（1 mg/kg）细菌脂多糖（LPS）的大鼠的肾脏和肺中观察到不同的Cx基因Cx43的表达增加。为了阐明炎症期间 Cx43 表达增加的可能机制，克隆了该基因的 5' 侧翼区域并与报告基因（人生长激素）偶联。该构建体被转染到肾源性细胞 (NRK) 中，该细胞组成型表达 Cx43。确实在克隆区域中发现了Cx43启动子活性，该区域包含Cx43基因转录起始位点上游的725个碱基对。发现通过将转染的细胞与从LPS处理的大鼠获得的血清一起温育，Cx43启动子活性增加。此外，观察到转染细胞与LPS或白细胞介素1β直接孵育，但不与其他细胞因子一起孵育，可增加Cx43启动子活性。这些结果表明，施用 LPS 后 Cx43 的表达是炎症反应的一部分。此外，该基因的表达似乎是由促炎介质介导的。
At the molecular level, the inflammatory response is characterized by changes in gene expression of various organ systems. One gene by which expression has been observed to be altered in the liver during inflammation is connexin (Gx) 32. Ox genes encode the polypeptide subunits of the hemichannels that comprise gap junctions. In the present study, an increase in the expression of a different Cx gene, Cx43, was observed in the kidney and lung of rats injected with a sublethal dose (1 mg/kg) of bacterial lipolysaccharide (LPS). To elucidate the possible mechanism by which the Cx43 expression is increased during inflammation, the 5' flanking region of the gene was cloned and coupled to a reporter gene (human growth hormone). This construct was transfected into cells of renal origin (NRK), which express Cx43 constitutively. The Cx43 promoter activity was indeed found in the cloned region, which contained 725 base pairs upstream of the transcriptional initiation site of the Cx43 gene. The Cx43 promoter activity was found to be increased by incubation of the transfected cells with serum obtained from LPS-treated rats. Moreover, direct incubation of the transfected cells with LPS or interleukin 1 beta, but not with other cytokines, was observed to increase the Cx43 promoter activity. These results suggest the expression of Cx43 after administration of LPS is part of the inflammatory response. Moreover, the expression of this gene seems to be mediated by proinflammatory mediators.