Abstract
The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR) mediates HCO3 - and Cl- secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3 - and Cl- secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (Isc) techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3 - and Cl- secretions in mice, but forskolin-stimulated HCO3 - and Cl- secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001). The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001), and the mRNA and protein expression levels of tumor necrosis factor α (TNFα) were markedly increased in donor jejunal mucosae of mice (P<0.001), compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα.
Highlights
Intestinal transplantation is currently accepted as a potential therapeutic option for patients with irreversible intestinal failure, including those with short bowel syndrome, who have lifethreatening total parental nutrition complications, e.g. total parental nutrition-related liver dysfunction and difficulty of central venous access
In addition to CFTR, solute carrier family 26 member a3 (Slc26a3) and solute carrier family 26 member a6 (Slc26a6) are two major Cl2/HCO3exchangers and regulate Cl- and HCO3- transports of intestinal epithelial cells [17]
We further examined the mRNA and protein expressions of Slc26a3 and Slc26a6 in donor and recipient jejunal mucosae after heterotopic jejunal transplantation
Summary
Intestinal transplantation is currently accepted as a potential therapeutic option for patients with irreversible intestinal failure, including those with short bowel syndrome, who have lifethreatening total parental nutrition complications, e.g. total parental nutrition-related liver dysfunction and difficulty of central venous access. The secretion and absorption of intestine is the most important physiological function of intestine. The secretion and absorption function of intestinal graft is one of the most important factors for successful intestinal transplantation. The studies have demonstrated that intestinal absorptive function has been impaired following small intestinal transplantation [5,6], and the defects in intestinal absorptive function occur even in nonrejecting small intestinal grafts [7,8]. Intestinal secretion function after intestinal transplantation is poorly understood. Intestinal secretion aids digestion and absorption, and occurs as a result of some pathophysiologic processes. Intestinal secretion results from the active transports of two principal ions, Cl- and HCO3- [9]. CFTR, which mediates Cl- and HCO3- transports, plays an important role in the regulation of intestinal secretion function [9,12]
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