Sipos Ferenc, Muzes Györgyi, Valcz Gábor, Galamb Orsolya, Tóth Kinga, Leiszter Katalin, Krenács Tibor, Tulassay Zsolt, Molnár Béla
2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Scand J Gastroenterol. 2010 Apr;45(4):440-8. doi: 10.3109/00365521003624144.
Mesenchymal-epithelial transition may have crucial role in mucosal regeneration, hence we assayed epithelial growth factor receptor (EGFR), insulin-like growth factor receptor-1 (IGF1R), hepatocyte-derived growth factor receptor (HGFR), CDX2 and cytokeratin (CK) expression in lymphoid aggregates (LA) of ulcerative colitis (UC).
Tissue microarrays (TMAs) made of biopsy samples from 20 mildly, 20 moderately and 20 severely active UC, 12 non-specific colitis (NSC) and 20 healthy colon were prepared, and immunolabelled with anti-EGFR, -IGF1R, -HGFR, -CDX2, -CK antibodies. After virtual microscopic evaluation, one-way ANOVA and correlation analysis were performed. For validation, TaqMan real-time RT-PCR was performed by using RNA from laser microdissected LA from 10 healthy colon and 10 endoscopically active UC biopsies.
The number of LA was in tight positive correlation with the severity of inflammation (r=0.9). The number of EGFR/HGFR positive subepithelial cells was found to be significantly elevated in severe (21.6+/-2.1%/21.3+/-1.9%), moderate (14.3+/-1.7%/14.6+/-1.6%) and mild (7.2+/-1.6%/7.4+/-1.3%) inflammation compared to healthy colon mucosa (2.6+/-1.4%/2.4+/-1.03%) (p < 0.005). Some alterations were found between UC and NSC samples regarding EGFR and HGFR expression. IGF1R immunoreactive cells were only found in a trace number in all cases. Increasing trend of CDX2 and CK positive subepithelial cells was found in active UC, but it was not in significant correlation with the severity of inflammation.
EGFR and HGFR positive subepithelial cells in LA may be involved in the induction of the regenerative mucosal processes. The presence of CDX2/CK positive subepithelial cells suggests that mesenchymal-to-epithelial transition may be located to lymphoid aggregates.
间充质-上皮转化可能在黏膜再生中起关键作用，因此我们检测了溃疡性结肠炎（UC）淋巴样聚集物（LA）中上皮生长因子受体（EGFR）、胰岛素样生长因子受体-1（IGF1R）、肝细胞衍生生长因子受体（HGFR）、CDX2和细胞角蛋白（CK）的表达。
制备由20例轻度、20例中度和20例重度活动期UC、12例非特异性结肠炎（NSC）和20例健康结肠活检样本制成的组织微阵列（TMA），并用抗EGFR、-IGF1R、-HGFR、-CDX2、-CK抗体进行免疫标记。经过虚拟显微镜评估后，进行单因素方差分析和相关性分析。为进行验证，使用来自10例健康结肠和10例内镜下活动期UC活检组织的激光显微切割LA的RNA进行TaqMan实时逆转录聚合酶链反应。
LA的数量与炎症严重程度呈紧密正相关（r = 0.9）。与健康结肠黏膜（2.6±1.4%/2.4±1.03%）相比，在重度（21.6±2.1%/21.3±1.9%）、中度（14.3±1.7%/14.6±1.6%）和轻度（7.2±1.6%/7.4±1.3%）炎症中，EGFR/HGFR阳性上皮下细胞数量显著升高（p < 0.005）。在UC和NSC样本之间，关于EGFR和HGFR表达发现了一些差异。在所有病例中仅发现痕量的IGF1R免疫反应性细胞。在活动期UC中发现CDX2和CK阳性上皮下细胞有增加趋势，但与炎症严重程度无显著相关性。
LA中EGFR和HGFR阳性上皮下细胞可能参与再生性黏膜过程的诱导。CDX2/CK阳性上皮下细胞的存在表明间充质-上皮转化可能定位于淋巴样聚集物。
