Obstructive Jaundice Alters CD44 Expression in Rat Small Intestine

Abstract

Hypothesis: CD44 is an adhesion molecule expressed by neutrophils, lymphocytes and epithelial cells. CD44 is involved in cell-cell and cell-matrix binding. In addition to lymphocyte trafficking, CD44 also plays a crucial role in the maintenance of intestinal villus integrity. We hypothesize that obstructive jaundice may alter CD44 expression in the rat small intestine and oral glutamine intake can restore the altered CD44 expression in the small intestine of the rat undergoing obstructive jaundice. Materials and Methods: In a prospective animal model study at a university hospital, 41 Sprague-Dawley rats were randomized to 4 groups. Group A (n = 13, control) underwent a sham operation. Group B (n = 12, obstructive jaundice for 1 week) underwent common bile duct ligation. Group C (n = 8, obstructive jaundice for 2 weeks) underwent common bile duct ligation. Group D (n = 8, obstructive jaundice for 2 weeks) underwent common bile duct ligation with oral glutamine intake daily. After 1 and 2 weeks, segments of the proximal jejunum and distal ileum were harvested from groups A and B and groups C and D, respectively. Immunohistochemical expression of CD44 on the cell surface was then evaluated and recorded. Comparisons among the 4 groups were performed. Results: In the 1-week obstructive jaundice group, 173.8 ± 24.0 cells/1,000 enterocytes of the proximal jejunum expressed surface CD44, while 137.0 ± 13.8 cells were stained in the control group (p < 0.001). In the 1-week obstructive jaundice group, 169.8 ± 20.7 cells/1,000 enterocytes of the distal ileum expressed surface CD44, while 119.5 ± 20.8 cells were stained in the control group (p < 0.001). In the 2-week obstructive jaundice group, the number of cells expressing surface CD44 were significantly decreased both in jejunum (112.1 ± 17.0, p = 0.002) and ileum (100.1 ± 12.5, p = 0.028) when compared with those of the control group. With daily oral glutamine intake in group D, the number of cells expressing surface CD44 in the jejunum (149.3 ± 29.7) was restored to that of the control group (p = 0.302) and the number of cells expressing surface CD44 in the ileum (140.4 ± 23.0) was even higher than that of the control group (p = 0.045). Conclusion: Obstructive jaundice for 1 week initially upgraded CD44 expression in the rat small intestine and the CD44 expression later became significantly depressed after obstructive jaundice for 2 weeks. Oral glutamine intake daily could effectively restore the CD44 expression in the small intestine of the rat undergoing obstructive jaundice for 2 weeks.

Effect of Vitamin A on the CD44 Expression in the Small Intestine of Rats with Obstructive Jaundice

“…This distribution of the CD44 expression corresponds to that of the regions of the epithelium undergoing cell division [9,10] . When any pathological condition (such as ischemia-reperfusion injury, obstructive jaundice, immunological bowel disease, and small-bowel allograft rejection) occurs in the gut, the CD44 expression is affected, thus immune and barrier functions of the mucosa are impaired [7,[19][20][21] . It has been reported [10] that the regulatory mechanisms and the physiological role underlying the expression of CD44 on intestinal epithelial cells may be due to the localized production of cytokines such as interferon gamma and tumor necrosis factor alpha.…”

“…It has been reported [10] that the regulatory mechanisms and the physiological role underlying the expression of CD44 on intestinal epithelial cells may be due to the localized production of cytokines such as interferon gamma and tumor necrosis factor alpha. Sheen-Chen et al [7] demonstrated that 1 week of obstructive jaundice initially upgraded the CD44 expression in the rat small intestine, but after 2 weeks the CD44 expression became significantly decreased. We found similar results with respect to the CD44 expression in the rat small intestine after 2 weeks of obstructive jaundice.…”

“…CD44 has been known to function as a cell surface adhesion receptor, mediating both cell-cell and cell-matrix binding, and is derived from a single gene located on chromosome 11 [7,8] . Although in the normal small intestine, the expression of CD44 is seen on many different cells within the lamina propria, its expression on epithelial cells is restricted to the region of cell division at the base of the crypts [9] .…”

Z-LLY-FMK Attenuates Intestinal Apoptosis After Bile Duct Ligation in Rats

“…Using sterile techniques, a mid-line incision was made, the common bile duct was identified, double-ligated with 5-0 silk, and divided between the two ligatures [17][18][19][20][21][22][23]. Shamoperated animals had the common bile duct freed from the surrounding soft tissue without ligation and transection.…”

Z-LLY-FMK Can Attenuate Hepatocyte Apoptosis After Bile Duct Ligation in Rat

“…Using sterile techniques, a mid-line incision was made, and the common bile duct was identified, double-ligated with 5-0 silk, and divided between the two ligatures [16][17][18][19][20]. Sham-operated animals had the common bile duct freed from the surrounding soft tissue without ligation and transection.…”