Abstract
PTPN2 is a risk gene for Crohn's disease (CD). We investigated whether PTPN2 genetic variants (rs2542151 and rs2542152) were associated with CD in a familial IBD registry. Both rs2542151 and rs2542152 are associated with CD, but not ulcerative colitis (UC). mRNA expression levels of PTPN2 were significantly increased in intestinal tissues (p=0.0493), and nearly significantly increased in B cells (p=0.0889) from CD patients, but not significantly altered in UC. cDNA microarray results found that PTPN2 was down-regulated by NKX2-3 knockdown in human cells. We confirmed this observation by RT-PCR analyses in NKX2-3 knockdown in B cells from IBD patients and human intestinal microvascular endothelial cells (HIMEC). In addition, we found that mRNA expression of another IBD-associated gene, NKX2-3, was increased in intestinal tissues and B cells from CD patients, but not significantly increased in UC patients. A positive correlation was observed between mRNA expression of PTPN2 and NKX2-3 in B cells and in intestinal tissues from both CD and UC patients. These results suggest that PTPN2 may have an important role in CD pathogenesis and may represent a potential diagnostic and therapeutic target for IBD.
Highlights
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, primarily comprised of Crohn’s disease (CD) and ulcerative colitis (UC)
single nucleotide polymorphism (SNP) rs2542152 demonstrated a protective effect on IBD since the frequency of homozygous polymorphism (CC) in the CD patients (9.1%) was lower than in the controls (19.9%) (Table 1b). rs2542152 was not associated with UC (p > 0.05)
We examined mRNA and protein expression of PTPN2 in NKX2-3 knockdown cells. mRNA and protein expression levels of PTPN2 were significantly decreased by NKX2-3 knockdown in a B cell line from a CD patient, a B cell line from a UC patient, and a human intestinal microvascular endothelial cells (HIMEC) line (Fig. 3B and 3C)
Summary
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, primarily comprised of Crohn’s disease (CD) and ulcerative colitis (UC). Of the PTPN2 gene (protein tyrosine phosphatase, nonreceptor type 2), with CD [2] This association has been replicated by several follow-up studies [3,4,5]; a functional role for PTPN2 in CD pathogenesis remains unclear. Our cDNA microarray data showed that PTPN2 expression is down-regulated following knockdown of NKX2-3 in B cells from IBD patients [11,12] and human intestinal microvascular endothelial cells (HIMEC) [13]. As this indicated that PTPN2 gene expression might be regulated by NKX2-3, we compared PTPN2 expression levels with expression of NKX2-3 in IBD patients
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