The arthritis severity locus Cia5a regulates the expression of inflammatory mediators including Syk pathway genes and proteases in pristane-induced arthritis.
The arthritis severity locus Cia5a regulates the expression of inflammatory mediators including Syk pathway genes and proteases in pristane-induced arthritis.
复制标题
DOI：
10.1186/1471-2164-13-710
复制
发表时间：
2012-12-19
期刊：
影响因子：
4.4
通讯作者：
Gulko PS
中科院分区：
文献类型：
--
作者：
Brenner M;Gulko PS
Cia5a 是大鼠 10 号染色体上的一个位点，在两种类风湿关节炎（胶原诱导性关节炎和降植烷诱导性关节炎 (PIA)）模型中调节疾病严重程度和关节损伤。在本研究中，我们旨在通过基于微阵列的基因表达分析，对 MHC 相同的 DA（重度糜烂性疾病）和 DA.F344(Cia5a) 同源性（轻度非糜烂性疾病）大鼠的滑膜组织进行基因表达来鉴定受 Cia5a 调节的细胞和分子过程。在诱导 PIA 21 天后，使用 Illumina RatRef-12 BeadChip（21,922 个基因）对来自 6 只 DA 和 8 只 DA.F344(Cia5a) 大鼠的滑膜组织进行分析，并通过 qPCR 确认所选数据。滑膜组织中促炎介质的表达显着增加，例如 Il1b（5 倍）、Il18（3.9 倍）、Cxcl1（10 倍）、Cxcl13（7.5 倍）和 Ccl7（7.9 倍），以及 Mmp3（23 倍）、Mmp9（32 倍）、Mmp14（4.4 倍）和组织蛋白酶等蛋白酶。 DA，同源基因的水平相应降低。与 DA.F344(Cia5a) 相比，DA 滑膜组织中脾酪氨酸激酶 (Syk) 通路 47 个成员的 mRNA 水平显着升高，其中包括 Syk（5.4 倍）、Syk 激活受体和相互作用蛋白，以及受 Syk 调节的基因，如 NFkB 和 NAPDH 氧化酶复合物基因。受保护的同源基因中，Rxrg、Pparg 和 Rev-erba 等核受体 (NR) 增加，抗炎 NR 靶基因 Scd1 也增加（增加 54 倍）。 Tnn（减少 72 倍）是 DA 中增加最显着的基因。对滑膜组织中基因表达的分析表明，关节炎严重程度位点 Cia5a 调节炎症和关节损伤关键介质的表达，以及 Syk 通路成员的表达。这种表达模式与疾病的严重程度和关节损伤相关，并且与 Cia5a 的基因一起可能成为有用的生物标志物，用于识别患有严重和糜烂性疾病风险增加的患者。 Cia5a 基因的鉴定有可能为治疗和预后产生新的重要靶标。
Cia5a is a locus on rat chromosome 10 that regulates disease severity and joint damage in two models of rheumatoid arthritis, collagen- and pristane-induced arthritis (PIA). In this study, we aimed to identify cellular and molecular processes regulated by Cia5a using microarray-based gene expression analysis of synovial tissues from MHC identical DA (severe erosive disease) and DA.F344(Cia5a) congenics (mild non-erosive disease) rats. Synovial tissues from six DA and eight DA.F344(Cia5a) rats were analyzed 21 days after the induction of PIA using the Illumina RatRef-12 BeadChip (21,922 genes) and selected data confirmed with qPCR. There was a significantly increased expression of pro-inflammatory mediators such as Il1b (5-fold), Il18 (3.9-fold), Cxcl1 (10-fold), Cxcl13 (7.5-fold) and Ccl7 (7.9-fold), and proteases like Mmp3 (23-fold), Mmp9 (32-fold), Mmp14 (4.4-fold) and cathepsins in synovial tissues from DA, with reciprocally reduced levels in congenics. mRNA levels of 47 members of the Spleen Tyrosine Kinase (Syk) pathway were significantly increased in DA synovial tissues compared with DA.F344(Cia5a), and included Syk (5.4-fold), Syk-activating receptors and interacting proteins, and genes regulated by Syk such as NFkB, and NAPDH oxidase complex genes. Nuclear receptors (NR) such as Rxrg, Pparg and Rev-erba were increased in the protected congenics, and so was the anti-inflammatory NR-target gene Scd1 (54-fold increase). Tnn (72-fold decrease) was the gene most significantly increased in DA. Analyses of gene expression in synovial tissues revealed that the arthritis severity locus Cia5a regulates the expression of key mediators of inflammation and joint damage, as well as the expression of members of the Syk pathway. This expression pattern correlates with disease severity and joint damage and along with the gene accounting for Cia5a could become a useful biomarker to identify patients at increased risk for severe and erosive disease. The identification of the gene accounting for Cia5a has the potential to generate a new and important target for therapy and prognosis.
登录
查看更多内容
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
32.4
作者：
Hill, Jonathan A.;Feuerer, Markus;Benoist, Christophe
通讯作者：
Benoist, Christophe
影响因子：
30.5
作者：
Karp, CL;Grupe, A;Wills-Karp, M
通讯作者：
Wills-Karp, M
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
--
作者：
Jakus, Zoltan;Simon, Edina;Balazs, Balint;Mocsai, Attila
通讯作者：
Mocsai, Attila