Bajaj-Elliott M, Breese E, Poulsom R, Fairclough P D, MacDonald T T
Department of Pediatric Gastroenterology, St. Bartholomews, London, United Kingdom.
Am J Pathol. 1997 Nov;151(5):1469-76.
Inflammation in the gastrointestinal tract is associated with increased epithelial cell proliferation. Keratinocyte growth factor (KGF) is an epithelial cell mitogen widely expressed by mesenchymal cells subjacent to the epithelial cells. In this study, we have investigated the expression and distribution of KGF in normal and diseased (Crohn's disease and ulcerative colitis(UC)) intestine by quantitative competitive reverse-transcriptase polymerase chain reaction in whole biopsies and purified lamina propria myofibroblasts and by in situ hybridization. Analysis of whole mucosal biopsies reveals significantly higher numbers of KGF mRNA transcripts in UC compared with Crohn's colitis and control colon (P < 0.001). KGF transcripts were also elevated in Crohn's ileitis compared with normal ileum. In situ hybridization showed a marked increase in cells expressing KGF mRNA throughout the lamina propria in both UC and Crohn's tissue. In Crohn's disease, positively hybridizing cells were only rarely seen in the submucosa but were abundant around the bases of the crypts and were not associated with lymphoid aggregates. In purified mucosal myofibroblasts, increased (15- to 20-fold) KGF mRNA expression was seen in UC compared with control and Crohn's tissue. These results confirm and extend earlier studies showing that KGF transcripts are elevated in inflammatory bowel disease, but they show for the first time that transcripts are higher in UC than Crohn's disease because of increased production by mucosal mesenchymal cells.
胃肠道炎症与上皮细胞增殖增加有关。角质形成细胞生长因子(KGF)是一种上皮细胞有丝分裂原,由上皮细胞下方的间充质细胞广泛表达。在本研究中,我们通过对全层活检组织及纯化的固有层肌成纤维细胞进行定量竞争性逆转录-聚合酶链反应以及原位杂交,研究了KGF在正常及患病(克罗恩病和溃疡性结肠炎(UC))肠道中的表达和分布。对全层黏膜活检组织的分析显示,与克罗恩结肠炎和对照结肠相比,UC中KGF mRNA转录本的数量显著更高(P < 0.001)。与正常回肠相比,克罗恩回肠炎中的KGF转录本也有所升高。原位杂交显示,在UC和克罗恩病组织的整个固有层中,表达KGF mRNA的细胞显著增加。在克罗恩病中,黏膜下层仅偶尔可见阳性杂交细胞,但在隐窝底部周围大量存在,且与淋巴聚集物无关。在纯化的黏膜肌成纤维细胞中,与对照和克罗恩病组织相比,UC中KGF mRNA表达增加(15至20倍)。这些结果证实并扩展了早期研究,表明KGF转录本在炎症性肠病中升高,但首次表明由于黏膜间充质细胞产生增加,UC中的转录本高于克罗恩病。