Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
J Biochem. 2013 Sep;154(3):265-73. doi: 10.1093/jb/mvt050. Epub 2013 May 27.
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 both in vivo in rat liver and in vitro in 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.
人甘露聚糖结合凝集素（MBL）由 MBL2 基因编码，是先天免疫的关键因子。然而，MBL2 的转录调控机制在很大程度上尚不清楚。过氧化物酶体增殖物激活受体（PPARs）是配体激活的转录因子，在许多生物学反应中发挥重要作用，包括脂质稳态、免疫功能和脂肪生成。在这项研究中，我们表明 PPARα 和 PPARγ 上调人 MBL2 的表达。通过荧光素酶测定、电泳迁移率变动分析和染色质免疫沉淀分析，我们证明 PPARs 通过过氧化物酶体增殖物反应元件（PPRE）调节人 MBL2 的表达。另一方面，PPARα 配体在体内大鼠肝脏和体外大鼠 H4IIE 肝癌细胞中均未影响 MBL2 mRNA 的表达。因此，PPAR 对人和啮齿动物 MBL2 基因表达的调控存在种属差异。我们还表明，对 PPAR 的反应的种属差异部分可能是由于 MBL2 启动子区域的 PPRE 中的序列特异性差异所致。这些结果表明，人 MBL2 的表达而非大鼠 MBL2 的表达受 PPAR 通过 PPRE 调节。
