c-Jun and c-Fos regulate the complement factor H promoter in murine astrocytes.
c-Jun and c-Fos regulate the complement factor H promoter in murine astrocytes.
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DOI：
10.1016/j.molimm.2011.08.013
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Martin BK
中科院分区：
文献类型：
--
作者：
Fraczek LA;Martin CB;Martin BK
补体系统是先天免疫的关键组成部分，需要调节以避免不适当的激活。这种调节由许多蛋白质提供，包括补体因子H（CFH），其是补体激活的旁路途径的关键调节剂。考虑到其调节功能，CFH中的突变已经涉及诸如年龄相关性黄斑变性和膜增生性肾小球肾炎的疾病，以及诸如阿尔茨海默病、帕金森病和脱髓鞘鼠模型、实验性自身免疫性脑脊髓炎（EAE）的中枢神经系统疾病。CFH在脑和中枢神经系统中的转录调控研究较少。我们的研究表明，CFH mRNA存在于几种CNS细胞类型。克隆小鼠CFH（mCFH）启动子，并通过截短结构进行检查，我们发现，在整个启动子的特定区域包含增强子和抑制剂，在星形胶质细胞中的炎性细胞因子的正调控。这些区域的数据库挖掘表明转录因子结合位点在不同物种之间是保守的，这导致了在-416 bp到-175 bp的241个碱基对（bp）区域中特异性转录因子结合相互作用的研究，该区域显示出最强的活性。通过超移位分析，确定c-Jun和c-Fos与该区域中星形胶质细胞中的CFH启动子相互作用。这些结果表明细胞周期和补体调节之间的关系，以及这些转录因子和CFH如何影响疾病将是一个有价值的研究领域。
The complement system is a critical component of innate immunity that requires regulation to avoid inappropriate activation. This regulation is provided by many proteins, including complement factor H (CFH), a critical regulator of the alternative pathway of complement activation. Given its regulatory function, mutations in CFH have been implicated in diseases such as age-related macular degeneration and membranoproliferative glomerulonephritis, and central nervous system diseases such as Alzheimer’s disease, Parkinson’s disease, and a demyelinating murine model, experimental autoimmune encephalomyelitis (EAE). There have been few investigations on the transcriptional regulation of CFH in the brain and CNS. Our studies show that CFH mRNA is present in several CNS cell types. The murine CFH (mCFH) promoter was cloned and examined through truncation constructs and we show that specific regions throughout the promoter contain enhancers and repressors that are positively regulated by inflammatory cytokines in astrocytes. Database mining of these regions indicated transcription factor binding sites conserved between different species, which led to the investigation of specific transcription factor binding interactions in a 241 base pair (bp) region at −416 bp to −175 bp that showed the strongest activity. Through supershift analysis it was determined that c-Jun and c-Fos interact with the CFH promoter in astrocytes in this region. These results suggest a relationship between cell cycle and complement regulation, and how these transcription factors and CFH affect disease will be a valuable area of investigation.
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影响因子：
4.7
作者：
Constantinescu, CS;Tani, M;Rostami, A
通讯作者：
Rostami, A
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
4.4
作者：
Ajona, Daniel;Hsu, Yi-Fan;Pio, Ruben
通讯作者：
Pio, Ruben
影响因子：
3
作者：
GORDON, DL;AVERY, VM;SADLON, TA
通讯作者：
SADLON, TA
影响因子：
4.6
作者：
Friese, MA;Manuelian, T;Zipfel, PF
通讯作者：
Zipfel, PF