AIM： To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease （IBD）. METHODS： To identify potential susceptibility genes we performed global gene...AIM： To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease （IBD）. METHODS： To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis （UC） and Crohn＇s disease （CD） compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed. RESULTS： We could show that aquaporin-8 （AQP8） mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQPS, however, revealed no mutations or polymorphisms in IBD patients. CONCLUSION： Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflao mmation and ulceration.展开更多
AIM： To determine free and conjugated serum bile acid （BA） levels in inflammatory bowel disease （IBD） subgroups with defined clinical manifestations. METHODS： Comprehensive serum BA profiling was performed in 35...AIM： To determine free and conjugated serum bile acid （BA） levels in inflammatory bowel disease （IBD） subgroups with defined clinical manifestations. METHODS： Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy con- trols by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. RESULTS： Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the second- ary BA lithocholic acid （LCA）, was increased significantly in Crohn＇s disease （CD） and ulcerative colitis （UC）, while most other serum BA species were decreased signifi- cantly. Total BA, total BA conjugate, and total BA glyco- conjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as signifi- cantly increased as the secondary BAs LCA, ursodeoxy- cholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode- oxycholic acid, were increased significantly compared to controls and patients without surgical interventions. CONCLUSION： Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diag- nostic characterization and differentiation of IBD sub- groups with defined clinical manifestations.展开更多
文摘AIM： To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease （IBD）. METHODS： To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis （UC） and Crohn＇s disease （CD） compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed. RESULTS： We could show that aquaporin-8 （AQP8） mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQPS, however, revealed no mutations or polymorphisms in IBD patients. CONCLUSION： Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflao mmation and ulceration.
基金Supported by A grant from the Deutsche Forschungs-gemeinschaft (SFB585-A1/A4)the Stiftung für Pathobio-chemie und Molekulare Diagnostik (TL),the Dietmar Hopp Foundation+4 种基金the EU FP 6 funded SSA "ELIfe" project (The Eu-ropean Lipidomics InitiativeShaping the life sciences proposal number 013032)the EU FP 7 funded project "Lipidomic-Net" (lipid droplets as dynamic organelles of fat deposition and release:translational research towards human diseaseproposal number 202272)
文摘AIM： To determine free and conjugated serum bile acid （BA） levels in inflammatory bowel disease （IBD） subgroups with defined clinical manifestations. METHODS： Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy con- trols by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. RESULTS： Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the second- ary BA lithocholic acid （LCA）, was increased significantly in Crohn＇s disease （CD） and ulcerative colitis （UC）, while most other serum BA species were decreased signifi- cantly. Total BA, total BA conjugate, and total BA glyco- conjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as signifi- cantly increased as the secondary BAs LCA, ursodeoxy- cholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode- oxycholic acid, were increased significantly compared to controls and patients without surgical interventions. CONCLUSION： Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diag- nostic characterization and differentiation of IBD sub- groups with defined clinical manifestations.
