Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation.
Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation.
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Claudin-1和Claudin-2表达在炎症性肠病中升高，可能有助于早期的肿瘤转化。
DOI：
10.1038/labinvest.2008.78
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发表时间：
2008-10
影响因子：
5
通讯作者：
Turner, Jerrold R.
中科院分区：
文献类型：
--
作者：
Weber, Christopher R.;Nalle, Sam C.;Tretiakova, Maria;Rubin, David T.;Turner, Jerrold R.
炎症性肠病（IBD）患者发生结直肠腺癌的风险增加。导致IBD相关致癌作用的因素尚不清楚。我们推测肠上皮紧密连接蛋白表达的改变可能有助于肿瘤的进展。使用人类活检的半定量免疫组织化学染色来评估紧密连接蛋白claudin-1、claudin-2、claudin-4和occludin在IBD、IBD相关异型增生、急性自限性结肠炎（ASLC）和散发性腺瘤中的表达。Claudin-1和claudin-2表达在活动性IBD、腺瘤和IBD相关异型增生中升高，但在ASLC中不升高。相比之下，claudin-4表达在活动性IBD和ASLC中均升高。在所有情况下，Occludin表达与对照相似。重要的是，在IBD中，claudin-1和claudin-2的表达与炎症活动呈正相关。为了研究改变的密蛋白表达的潜在机制，将β-连环蛋白活化评估为核定位。与claudin-1和claudin-2一样，β-catenin在IBD、异型增生、IBD相关异型增生中显著活化，而在ASLC中仅轻微活化。总之，这些数据表明β-连环蛋白转录活性在慢性损伤中升高，并且这可能有助于增加的密蛋白-1和密蛋白-2表达。我们推测claudin-1和claudin-2表达的增加可能参与IBD相关肿瘤转化的早期阶段。
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal adenocarcinoma. The factors that result in IBD-associated carcinogenesis are not understood. We hypothesized that altered expression of intestinal epithelial tight junction proteins might contribute to neoplastic progression. Semi-quantitative immunohistochemical staining of human biopsies was used to assess expression of the tight junction proteins claudin-1, claudin-2, claudin-4, and occludin in IBD, IBD-associated dysplasia, acute, self-limited colitis (ASLC), and sporadic adenomas. Claudin-1 and claudin-2 expression was elevated in active IBD, adenomas, and IBD-associated dysplasia, but not ASLC. In contrast, claudin-4 expression was elevated in both active IBD and ASLC. Occludin expression was similar to control in all cases. Importantly, in IBD, claudin-1 and claudin-2 expression correlated positively with inflammatory activity. To investigate mechanisms underlying altered claudin expression, β-catenin activation was assessed as nuclear localization. Like claudin-1 and claudin-2, β-catenin was markedly activated in IBD, dysplasia, IBD-associated dysplasia, but only slightly activated in ASLC. Taken together, these data suggest that β-catenin transcriptional activity is elevated in chronic injury and that this may contribute to increased claudin-1 and claudin-2 expression. We speculate that increased claudin-1 and claudin-2 expression may be involved in early stages of transformation in IBD-associated neoplasia.
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