Palmieri Orazio, Creanza Teresa M, Bossa Fabrizio, Palumbo Orazio, Maglietta Rosalia, Ancona Nicola, Corritore Giuseppe, Latiano Tiziana, Martino Giuseppina, Biscaglia Giuseppe, Scimeca Daniela, De Petris Michele P, Carella Massimo, Annese Vito, Andriulli Angelo, Latiano Anna
*Division of Gastroenterology, IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Italy; †Institute of Intelligent Systems for Automation, National Research Council, CNR-ISSIA Unit, Bari, Italy; ‡Medical Genetics Unit, IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Italy; §Innovation and Technological Development Unit, IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Italy; and ‖Gastroenterology Unit 2, AOU Careggi Hospital, Florence, Italy.
Inflamm Bowel Dis. 2015 Jun;21(6):1260-8. doi: 10.1097/MIB.0000000000000370.
Ulcerative colitis (UC) and Crohn's disease (CD) share some pathogenetic features. To provide new steps on the role of altered gene expression, and the involvement of gene networks, in the pathogenesis of these diseases, we performed a genome-wide analysis in 15 patients with CD and 14 patients with UC by comparing the RNA from inflamed and noninflamed colonic mucosa.
Two hundred ninety-eight differentially expressed genes in CD and 520 genes in UC were identified. By bioinformatic analyses, 34 pathways for CD, 6 of them enriched in noninflamed and 28 in inflamed tissues, and 19 pathways for UC, 17 in noninflamed and 2 in inflamed tissues, were also highlighted.
In CD, the pathways included genes associated with cytokines and cytokine receptors connection, response to external stimuli, activation of cell proliferation or differentiation, cell migration, apoptosis, and immune regulation. In UC, the pathways were associated with genes related to metabolic and catabolic processes, biosynthesis and interconversion processes, leukocyte migration, regulation of cell proliferation, and epithelial-to-mesenchymal transition.
In UC, the pattern of inflammation of colonic mucosa is due to a complex interaction network between host, gut microbiome, and diet, suggesting that bacterial products or endogenous synthetic/catabolic molecules contribute to impairment of the immune response, to breakdown of epithelial barrier, and to enhance the inflammatory process. In patients with CD, genes encoding a large variety of proteins, growth factors, cytokines, chemokines, and adhesion molecules may lead to uncontrolled inflammation with ensuing destruction of epithelial cells, inappropriate stimulation of antimicrobial and T cells differentiation, and inflammasome events.
溃疡性结肠炎（UC）和克罗恩病（CD）具有一些共同的发病机制特征。为了探究基因表达改变以及基因网络在这些疾病发病机制中的作用，我们通过比较15例CD患者和14例UC患者炎症和非炎症结肠黏膜的RNA，进行了全基因组分析。
确定了CD中298个差异表达基因和UC中520个基因。通过生物信息学分析，还突出显示了CD的34条通路，其中6条在非炎症组织中富集，28条在炎症组织中富集；UC的19条通路，17条在非炎症组织中富集，2条在炎症组织中富集。
在CD中，这些通路包括与细胞因子和细胞因子受体连接、对外界刺激的反应、细胞增殖或分化的激活、细胞迁移、凋亡和免疫调节相关的基因。在UC中，这些通路与代谢和分解代谢过程、生物合成和相互转化过程、白细胞迁移、细胞增殖调节以及上皮-间质转化相关基因有关。
在UC中，结肠黏膜的炎症模式是宿主、肠道微生物群和饮食之间复杂相互作用网络的结果，这表明细菌产物或内源性合成/分解代谢分子会导致免疫反应受损、上皮屏障破坏并加剧炎症过程。在CD患者中，编码多种蛋白质、生长因子、细胞因子、趋化因子和黏附分子的基因可能导致炎症失控，继而破坏上皮细胞，不适当刺激抗菌和T细胞分化以及引发炎性小体事件。
