Masuda Hideki, Takahashi Yasuo, Asai Satoshi, Takayama Tadatoshi
Third Department of Surgery, Nihon University School of Medicine, Tokyo, Japan.
J Surg Res. 2003 May 1;111(1):85-90. doi: 10.1016/s0022-4804(03)00046-5.
Ulcerative colitis (UC) is a multifactorial disorder of unknown etiology. Few studies have applied genome-wide gene expression analysis in colon tissue samples of UC. We report the analysis of mucosal gene expression in UC and noninflamed control specimens.
This study included 7 UC patients who received a total colectomy because of severe total colitis. Normal control colon tissues were obtained at least 10 cm from the area of pathology in 3 colon cancer patients. Ten colonic tissue samples (7 UC and 3 normal control samples) were subjected to high-density oligonucleotide array analysis. To compare differences in the level of gene expression between UC and control samples, Mann-Whitney U-test was used, with significance set at P < 0.05.
Twenty-five genes had a 3.0 approximately 23.4-fold higher mRNA expression in UC samples compared with normal samples, whereas three genes had a 3.0 approximately 3.4-fold lower expression in UC samples compared with normal samples. Two genes showing more than a 10-fold increase expression in UC samples were a macrophage metalloelastase (L23808) and a osteopontin (AF052124). It has been said that macrophage metalloelastase is related to ulcer formation of the intestine, whereas osteopontin plays an important role in the pathogenesis of systemic lupus erythematosus and rheumatoid arthritis.
Our present study supports the previous report that macrophage metalloelastase is related to ulcer formation of UC, and it also indicates the possibility that osteopontin plays an important role in the pathogenesis of UC via increased immune activity.
溃疡性结肠炎（UC）是一种病因不明的多因素疾病。很少有研究在UC的结肠组织样本中应用全基因组基因表达分析。我们报告了UC和非炎症对照标本中黏膜基因表达的分析。
本研究纳入了7例因严重全结肠炎接受全结肠切除术的UC患者。在3例结肠癌患者中，从距病理区域至少10 cm处获取正常对照结肠组织。对10份结肠组织样本（7份UC样本和3份正常对照样本）进行高密度寡核苷酸阵列分析。为比较UC样本和对照样本之间基因表达水平的差异，采用Mann-Whitney U检验，显著性设定为P < 0.05。
与正常样本相比，25个基因在UC样本中的mRNA表达高约3.0至23.4倍，而3个基因在UC样本中的表达比正常样本低约3.0至3.4倍。在UC样本中表达增加超过10倍的两个基因是巨噬细胞金属弹性蛋白酶（L23808）和骨桥蛋白（AF052124）。据说巨噬细胞金属弹性蛋白酶与肠道溃疡形成有关，而骨桥蛋白在系统性红斑狼疮和类风湿关节炎的发病机制中起重要作用。
我们目前的研究支持先前的报告，即巨噬细胞金属弹性蛋白酶与UC的溃疡形成有关，并且还表明骨桥蛋白可能通过增加免疫活性在UC的发病机制中起重要作用。
