Multifactorial patterns of gene expression in colonic epithelial cells predict disease phenotypes in experimental colitis.
Multifactorial patterns of gene expression in colonic epithelial cells predict disease phenotypes in experimental colitis.
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DOI：
10.1002/ibd.22923
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发表时间：
2012-11
影响因子：
4.9
通讯作者：
Kaetzel, Charlotte S.
中科院分区：
文献类型：
--
作者：
Frantz, Aubrey L.;Bruno, Maria E. C.;Rogier, Eric W.;Tuna, Halide;Cohen, Donald A.;Bondada, Subbarao;Chelvarajan, R. Lakshman;Brandon, J. Anthony;Jennings, C. Darrell;Kaetzel, Charlotte S.
关键词：
炎症性肠病(IBD)的发病机制很复杂，需要识别分子生物标志物。上皮细胞在维持肠道内环境稳定方面起着核心作用。我们先前在结肠上皮细胞(CEC)中确定了5个“标志性”生物标记物，它们可以预测克罗恩病的疾病表型。在这里，我们研究CEC生物标记物定义肠道炎症的机制和严重程度的能力。我们分析了DSS急性结肠炎和T细胞介导的慢性结肠炎小鼠CEC中RelA、A20、pIgR、TNF和MIP-2的表达。因子分析将5个生物标志物合并为2个多因素主成分(PC)。单个小鼠的PC评分与疾病严重程度相关。在两种结肠炎模型中，PC1对RelA、A20和pIgR的影响很大，而PC2对肿瘤坏死因子和MIP-2的影响很大，而其他生物标记物的作用因炎症的病因而异。疾病严重程度与DSS结肠炎患者PC2评分升高和T细胞转移性结肠炎患者PC1评分降低相关。PIgR下调是两种结肠炎模型中观察到的共同特征，并与pIgR细胞定位改变和不能转运IgA有关。对上皮性基因表达的多因素分析可能比检测IBD的单基因反应更有信息量。这些结果有助于了解CEC在IBD发病机制中的动态平衡和促炎作用，并提示生物标记物分析可能有助于评估IBD患者的治疗方案。
The pathogenesis of inflammatory bowel disease (IBD) is complex and the need to identify molecular biomarkers is critical. Epithelial cells play a central role in maintaining intestinal homeostasis. We previously identified 5 “signature” biomarkers in colonic epithelial cells (CEC) that are predictive of disease phenotype in Crohn’s disease. Here we investigate the ability of CEC biomarkers to define the mechanism and severity of intestinal inflammation. We analyzed expression of RelA, A20, pIgR, TNF and MIP-2 in CEC of mice with DSS acute colitis or T cell-mediated chronic colitis. Factor analysis was used to combine the 5 biomarkers into 2 multifactorial principal components (PCs). PC scores for individual mice were correlated with disease severity. For both colitis models, PC1 was strongly weighted toward RelA, A20 and pIgR, and PC2 was strongly weighted toward TNF and MIP-2, while the contributions of other biomarkers varied depending on the etiology of inflammation. Disease severity was correlated with elevated PC2 scores in DSS colitis and reduced PC1 scores in T cell transfer colitis. Down-regulation of pIgR was a common feature observed in both colitis models and was associated with altered cellular localization of pIgR and failure to transport IgA. A multifactorial analysis of epithelial gene expression may be more informative than examining single gene responses in IBD. These results provide insight into the homeostatic and pro-inflammatory functions of CEC in IBD pathogenesis and suggest that biomarker analysis could be useful for evaluating therapeutic options for IBD patients.
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影响因子：
8
作者：
Pasparakis, M.
通讯作者：
Pasparakis, M.
影响因子：
2.5
作者：
Cario, Elke
通讯作者：
Cario, Elke
影响因子：
64.8
作者：
Khor, Bernard;Gardet, Agnes;Xavier, Ramnik J.
通讯作者：
Xavier, Ramnik J.
DOI：
10.1073/pnas.88.19.8796
发表时间：
1991-10-01
影响因子：
11.1
作者：
KAETZEL, CS;ROBINSON, JK;LAMM, ME
通讯作者：
LAMM, ME
影响因子：
4.3
作者：
Kim, Tae Woon;Seo, Jae Nam;Oh, Kwon Ik
通讯作者：
Oh, Kwon Ik