Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet

Abstract

DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine)-fed mice are widely used as a model for cholestatic liver disease. We examined the expression of tight junction protein claudin subspecies by immunofluorescent histochemistry in small intestine and kidney tissues of mice fed a DDC diet for 12 weeks. In the small intestine, decreases in claudin-3, claudin-7 and claudin-15 were observed in villous epithelial cells corresponding to the severity of histological changes while leaving the abundance of these claudin subspecies unchanged in crypt cells. Nevertheless, the proliferative activity of intestinal crypt cells measured by immunohistochemistry for Ki-67 decreased in the mice fed the DDC diet compared with that of control mice. These results suggest the possibility that DDC feeding affects the barrier function of villous epithelial cells and thus inhibits the proliferative activity of crypt epithelial cells. On the other hand, in the kidney, remarkable changes were found in the subcellular localization of claudin subspecies in a segment-specific manner, although histological changes of renal epithelial cells were quite minimal. These results indicate that immunohistochemistry for claudin subspecies can serve as a useful tool for detecting minute functional alterations of intestinal and renal epithelial cells.

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3

“…In this study, we identified the expression of claudins 3, 4, 7, and 15 in the murine small and large intestine and in Caco-2 cells; however, only claudin 3 and 15 were downregulated and upregulated, respectively, in response to sucralose and aspartame treatment. Previous studies have demonstrated that dietary components, such as gluten, alter claudin 3 and 15 expression [ 45 , 46 ]; however, this is the first study to indicate that artificial sweeteners regulate these tight junction proteins. We further demonstrated the importance of claudin 3, rather than claudin 15, in regulating sweetener-induced permeability through T1R3.…”

Vitamin D Receptor Deletion Leads to the Destruction of Tight and Adherens Junctions in Lungs

“…The levels of claudin-3 and claudin-7 mRNA and proteins of lung tissues in VDR -/mice showed no significant alteration, compared to those in wild type mice. Interestingly, decreases of claudin-3, claudin-7 and claudin-15 proteins in the small intestine have been detected in villous epithelial cells corresponding to the severity of histological changes, whereas leaving these claudin subspecies unchanged in crypt cells 38 . These results suggested that claudins have different biology function in the different cells or tissues.…”

Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression

“…Studies in knockout mice have shown that claudin-15, which forms a paracellular cation channel, can compensate for loss of claudin-2 expression. 12, 16, 39 Despite these and other data indicating that function of claudin-15 is important, 13, 40–43 it has not been previously assessed in human disease. We therefore focused our analysis on claudins 2, 8, and 15 (Suppl.…”