Claudins comprise a multigene family of 24 species and have been shown to constitute the backbone of tight junction strands in simple epithelial cells and to be directly involved in their barrier functions. Apical-most
tight junction protein complexes (TJs) are implicated in
inflammatory bowel disease (IBD) pathophysiology. Except for
claudin-8, TJs explored in this study (including ZO-1,
claudin-1, -2, -3, -7, -12, and -15) were found to be expressed in rat colonic tissues. ZO-1 and claudin-7 were ubiquitously expressed in all study groups. As depicted in Fig. 1b, expressions of
claudin-2, -12, and -15 significantly diminished after combined treatment with
dextran sulfate sodium (DSS) and
busulfan (BU) (lane 5), compared with either agent alone (lanes 2 and 4). Despite the lack of significance, there appeared to be a subtle dose-dependent decrease with DSS treatment (lanes 2 and 3). In contrast to these results obtained from DSS
colitis, expression of
claudin-1 was significantly downregulated, while expression of
claudin-15 was upregulated in
colitis-associated cancer tissues in the
azoxymethane (AOM)/DSS model (Fig. 2b). It is very intriguing that
claudins' expression dynamics were mutually exclusive between
colitis and
colitis-associated cancer in rats. However, the
biological significance of disease-specific
claudin expression profiles will remain elusive until the specific expression and function of each
claudin in a tissue- and cell-type relationship are comprehensively clarified. Currently, the physiologic consequences of the diversity of TJ barrier function resulting from multiple combinations of
claudins are only beginning to be recognized. Full unraveling of these complexities could inspire a new paradigm of
inflammation and
cancer, and eventually translate to clinical practice on IBD.