TY - JOUR
T1 - Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies
T2 - Insights into distinctive pathogenesis
AU - Wu, Feng
AU - Dassopoulos, Themistocles
AU - Cope, Leslie
AU - Maitra, Anirban
AU - Brant, Steven R.
AU - Harris, Mary L.
AU - Bayless, Theodore M.
AU - Parmigiani, Giovanni
AU - Chakravarti, Shukti
PY - 2007/7/1
Y1 - 2007/7/1
N2 - Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies. Methods: To identify pathogenic processes underlying these disease subtypes, we used single endoscopic pinch biopsies to elucidate patterns of gene expression in active and inactive areas of UC and CD and compared these to infectious colitis and healthy control samples. Results: Unsupervised classification of a total of 36 samples yielded promising separation between the affected IBD, unaffected IBD, non-IBD colitis, and normal control samples, suggesting each sample type had a distinctive gene expression pattern. Genes differentially expressed in the CD samples compared to in the controls were related to IFNγ-inducible TH1 processes (IFITM1, IFITM3, STAT1, and STAT3) and antigen presentation (TAP1, PSME2, PSMB8). The most noticeable change in the UC samples was reduced expression of genes regulating biosynthesis, metabolism, and electrolyte transport (HNF4G, KLF5, AQP8, ATP2B1, and SLC16A). Twenty-five percent of genes down-regulated in the UC samples were also down-regulated in the infectious colitis samples. Unaffected biopsy samples of IBD patients also registered differences expression of genes compared to in the normal controls. Of these differentially expressed genes, only 2 were up-regulated, PSKH1, a regulator of mRNA processing, and PPID, a suppressor of apoptosis. Conclusions: The study shows that the gene expression patterns of IBD, CD in particular, are quite different from those of infectious colitis, highlighting distinctive expression of genes and pathways in UC and CD.
AB - Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies. Methods: To identify pathogenic processes underlying these disease subtypes, we used single endoscopic pinch biopsies to elucidate patterns of gene expression in active and inactive areas of UC and CD and compared these to infectious colitis and healthy control samples. Results: Unsupervised classification of a total of 36 samples yielded promising separation between the affected IBD, unaffected IBD, non-IBD colitis, and normal control samples, suggesting each sample type had a distinctive gene expression pattern. Genes differentially expressed in the CD samples compared to in the controls were related to IFNγ-inducible TH1 processes (IFITM1, IFITM3, STAT1, and STAT3) and antigen presentation (TAP1, PSME2, PSMB8). The most noticeable change in the UC samples was reduced expression of genes regulating biosynthesis, metabolism, and electrolyte transport (HNF4G, KLF5, AQP8, ATP2B1, and SLC16A). Twenty-five percent of genes down-regulated in the UC samples were also down-regulated in the infectious colitis samples. Unaffected biopsy samples of IBD patients also registered differences expression of genes compared to in the normal controls. Of these differentially expressed genes, only 2 were up-regulated, PSKH1, a regulator of mRNA processing, and PPID, a suppressor of apoptosis. Conclusions: The study shows that the gene expression patterns of IBD, CD in particular, are quite different from those of infectious colitis, highlighting distinctive expression of genes and pathways in UC and CD.
KW - Electrolyte transport
KW - Endoscopic pinch biopsy
KW - Gene expression pattern
KW - Immune response
KW - Inflammatory bowel disease
UR - http://www.scopus.com/inward/record.url?scp=34547621585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547621585&partnerID=8YFLogxK
U2 - 10.1002/ibd.20110
DO - 10.1002/ibd.20110
M3 - Article
C2 - 17262812
AN - SCOPUS:34547621585
VL - 13
SP - 807
EP - 821
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
SN - 1078-0998
IS - 7
ER -