Identification of RARRES1 as a core regulator in liver fibrosis
Identification of RARRES1 as a core regulator in liver fibrosis
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鉴定 RARRES1 作为肝纤维化的核心调节因子
DOI：
10.1007/s00109-012-0919-7
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Lammert F
中科院分区：
文献类型：
--
作者：
Teufel A;Becker D;Weber SN;Dooley S;Breitkopf-Heinlein K;Maass T;Hochrath K;Krupp M;Marquardt JU;Kolb M;Korn B;Niehrs C;Zimmermann T;Godoy P;Galle PR;Lammert F
遗传因素有助于肝纤维化的进展和调节。旨在识别纤维化发展关键调节因子的高通量基因组学/转录组学方法因难以将重要的生物“驱动因素”与修饰基因分开而受到污染。我们应用比较转录组学方法并研究了不同器官中的纤维化发展，以确定重叠的表达变化，因为这些基因可能是纤维化发展核心途径的一部分。对来自肝、肺和肾纤维化的公开微阵列数据进行基因表达分析。RARRES1、AGER和S100A2在所有纤维化实验中受到差异调节。通过先进的生物信息学分析和功能研究对 RARRES1 进行了广泛的分析。标准肝纤维化模型 (CCl4) 的微阵列和蛋白质印迹分析表明 RARRES1 mRNA 和蛋白质表达的早期诱导。此外，与非纤维化活检组织相比，晚期肝纤维化患者的组织样本中的定量 RT-PCR 显示出更高的表达。 RARRES1 过表达细胞的微阵列分析发现了与纤维化相关的主要特征的富集。此外，在肝星状细胞的体外激活过程中，RARRES1表达增加。为了进一步验证跨器官的促纤维化作用，我们证明了腺病毒 TGF-β1 诱导诱导的大鼠肺纤维化模型中 RARRES1 表达增加。我们进行了比较转录组学分析，以确定肝纤维化的核心途径，确认了一个候选基因，并阐明了其导致跨器官和物种纤维化的上下游机制。
Genetic factors contribute to progression and modulation of hepatic fibrosis. High throughput genomics/transcriptomics approaches aiming at identifying key regulators of fibrosis development are tainted with the difficulty of separating essential biological “driver” from modifier genes. We applied a comparative transcriptomics approach and investigated fibrosis development in different organs to identify overlapping expression changes, since these genes may be part of core pathways in fibrosis development. Gene expression was analysed on publicly available microarray data from liver, lung and kidney fibrosis.RARRES1,AGERandS100A2were differentially regulated in all fibrosis experiments. RARRES1 was extensively analysed by means of advanced bioinformatics analyses and functional studies. Microarray and Western Blot analysis of a standard liver fibrosis model (CCl4) demonstrated an early induction of RARRES1 mRNA and protein expression. In addition, quantitative RT-PCR in tissue samples from patients with advanced liver fibrosis showed higher expression as compared to non-fibrotic biopsies. Microarray analysis of RARRES1 overexpressing cells identified an enrichment of a major signature associated with fibrosis. Furthermore,RARRES1expression increased during in vitro activation of hepatic stellate cells. To further verify the pro-fibrogenic role across organs, we demonstrated an increase inRARRES1expression in a rat lung fibrosis model induced by adenoviral TGF-β1 induction. We have performed a comparative transcriptomics analysis in order to identify core pathways of liver fibrogenesis, confirmed a candidate gene and enlightened the up- and downstream mechanisms of its action leading to fibrosis across organs and species.
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影响因子：
5.8
作者：
Rodt T;von Falck C;Dettmer S;Halter R;Maus R;Ask K;Kolb M;Gauldie J;Länger F;Hoy L;Welte T;Galanski M;Maus UA;Borlak J
通讯作者：
Borlak J
人平滑肌细胞中钙结合 S100 蛋白的独特亚细胞定位及其响应细胞内钙升高的重新定位。
影响因子：
4
作者：
A. Mandinova;D. Atar;B. Schäfer;M. Spiess;U. Aebi;C. Heizmann
通讯作者：
C. Heizmann
影响因子：
8.4
作者：
Wu, CC;Shyu, RY;Jiang, SY
通讯作者：
Jiang, SY
影响因子：
14.9
作者：
Sherlock, G;Hernandez-Boussard, T;Cherry, JM
通讯作者：
Cherry, JM