| Co-Investigator(Kenkyū-buntansha) |
ASAI Satoshi Nihon University, School of Medicine, Associate Professor, 医学部, 助教授 (80231108)
TAKAHASHI Yasuo Nihon University, School of Medicine, Assistant, 医学部, 助手 (30339329)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
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 performed the analysis of gene expression in UC and noninflamed control specimens using high-density oligonucleotide array system (Affymetrix GeneChip^<【○!R】> System, Santa Clara, CA). In addition, using the antibody against the gene product that was expressed most remarkably in the colon tissue of UC, immunohistochemistry(IHC) study was performed in colon tissues of ulcerative colitis(UC), Crohn's disease(CD) and diverticulitis(Div) patients. Methods : To compare differences in the level of gene expression between UC and control samples, 10 colonic tissue samples (7 UC and 3 normal control samples) were subjected to high-density oligonucleotide array analysis. In addition, IHC staining study for the remarkable expressed gene product was performed in three groups : UC group, CD(Crohn's disease) group, Div(diverticulitis
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) group. Results : 1)Twenty five genes had a 3.0〜23.4-fold higher mRNA expression in UC samples compared with normal samples. Among the 25 genes, only two genes varied by more than 10-fold and a gene with the strongest expression was osteopontin(OPN). 2)Regarding OPN expression by IHC in intestinal epithelial cells, no difference was noted among the three groups. However, in the submucosa of the UC group, the ratio of two types of large cells (oval and spindle shape) expressing OPN was 61.2±14.4% (mean±SD), which was a significantly higher ratio than the CD group (14.9±7.0%) (p<0.05) and the Div group (11.2±6.1%) (p<0.05). In addition, the ratio of the UC group in the subserosa (50.1±15.0% )(mean±SD) was significantly higher than the CD group (16.9±6.2%) and Div group (12.6±5.7%). Based on the serial section study, oval shape cells were stained for anti-CD 68,while spindle shape cells were stained for anti-vimentin. Conclusion : Our present study indicates the possibility that osteopontin plays an important role in one of the pathogenesis of UC via increased immune activity. Less
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