Human mannose-binding lectin 2 is directly regulated by peroxisome proliferator-activated receptors (PPARs) via a peroxisome proliferator responsive element
Human mannose-binding lectin 2 is directly regulated by peroxisome proliferator-activated receptors (PPARs) via a peroxisome proliferator responsive element
复制标题
人甘露糖结合凝集素 2 由过氧化物酶体增殖物激活受体 (PPAR) 通过过氧化物酶体增殖物反应元件直接调节
DOI：
10.1093/jb/mvt050
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Doi T
中科院分区：
文献类型：
--
作者：
Tachibana K;Takeuchi K;Inada H;Sugimoto K;Ishimoto K;Yamashita M;Maegawa T;Yamasaki D;Osada S;Tanaka T;Rakug H;Hamakubo T;Sakai J;Kodama T;Doi T
人甘露糖结合凝集素（MBL）由MBL 2基因编码，是先天免疫的关键参与者。然而，MBL 2的转录调控机制在很大程度上是未知的。过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPARs）是一类配体激活的转录因子，在脂质平衡、免疫功能和脂肪形成等生物学反应中发挥重要作用。在这项研究中，我们发现，PPARα和PPARγ上调人MBL 2的表达。利用荧光素酶测定、电泳迁移率改变测定和染色质免疫沉淀测定，我们证明了PPARs通过过氧化物酶体增殖物反应元件（PPRE）调节人MBL 2的表达。而在大鼠肝内和体外培养的H4 IIE肝癌细胞中，MBL 2 mRNA的表达均不受PPARα配体的影响。因此，在人类和啮齿类动物之间，PPARs对MBL 2基因表达的调节存在物种差异。我们还表明，种属间对PPAR反应的差异可能部分是由于MBL 2启动子区中PPRE的序列特异性差异。这些结果表明，人而不是大鼠的MBL 2表达是由PPARs通过PPRE调节的。
Human mannose-binding lectin (MBL) is encoded by the MBL2 gene and is a key player in innate immunity. However, the mechanism of the transcriptional regulation of MBL2 is largely unknown. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play an important role in a number of biological responses, including lipid homeostasis, immune function and adipogenesis. In this study, we showed that PPARα and PPARγ up-regulate the expression of human MBL2. Using a luciferase assay, electrophoretic mobility-shift assay and chromatin immunoprecipitation assay, we demonstrated that PPARs regulate the expression of human MBL2 via the peroxisome proliferator responsive element (PPRE). On the other hand, MBL2 mRNA expression was not affected by the PPARα ligand bothin vivoin rat liver andin vitroin rat H4IIE hepatoma cells. Thus, there is a species difference in regulation of MBL2 gene expression by PPARs between humans and rodents. We also show that the species differences in response to PPAR could be due in part to sequence-specific differences in the PPRE in the promoter region of MBL2. These results indicate that human, but not rat, MBL2 expression is regulated by PPARs via a PPRE.