Expression and localization of pannexin-1 hemichannels in human colon in health and disease.

ABSTRACT

BACKGROUND: Pannexin-1 (Panx1) proteins can function as channels for adenosine triphosphate (ATP) release, but there have been limited studies investigating their potential role in the human intestine. The aim of this study was to characterize Panx1 expression and distribution in the human colon and its potential involvement in inflammatory bowel diseases (IBD). METHODS: Human colon segments were dissected into mucosa and muscularis layers, and evaluated for Panx1 expression by real-time PCR and Western blotting. Immunohistochemistry was conducted to localize the cellular distribution of Panx1 in intact tissues. KEY RESULTS: In the colonic muscularis of ulcerative colitis (UC), Panx1 mRNA expression showed a 3.5-fold reduction compared with control (P = 0.0015), but no change was seen in UC mucosa. In contrast, down-regulation of Panx1 mRNA was observed in both muscularis and mucosa of Crohn's disease (CD), showing a 2.7- and 1.8-fold reduction, respectively (P < 0.05). There was reduced Panx1 protein expression in CD muscularis, but no change in CD mucosa, UC muscularis, or UC mucosa. Pannexin-1 immunoreactivity was mainly localized to enteric ganglia, blood vessel endothelium, erythrocytes, epithelial cells, and goblet cells. Inflammatory bowel disease samples showed a similar overall pattern of Panx1 staining, but in UC myenteric ganglia, there was a significant reduction in Panx1 immunoreactivity. Significant Panx1 positive leukocyte infiltrations were seen at the sites of inflammation. CONCLUSIONS & INFERENCES The presence of Panx1 in the colon and changes to its distribution in disease suggests that Panx1 channels may play an important role in mediating gut function and in IBD pathophysiology.