Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia

Abstract

The expression of CDX2 precedes those of CDX1, sucrase-isomaltase, other intestine-specific genes (human defensin-5, alkaline phosphatase), and MUC2 during the progression of intestinal metaplasia. These findings imply that the expression of CDX2 may trigger the initiation and development of intestinal metaplasia.

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis

“…Functional studies have already shown CDX2 could regulate many intestine-specific gene transcription in vivo. Such like intestinal-type alkaline phosphatase (ALP); the well characterized brushborder enzyme, sucrase-isomaltase (SI), human defensin-5 (HD), and mucus-secreting goblet cell-mucin marker (MUC2) (Eda et al, 2002;Guo et al, 2004;Weimann et al, 2010). These genes control the differentiation of the IM of gastrointestinal tract.…”

Interaction of Toll-like receptors with bacterial components induces expression of CDX2 and MUC2 in rat biliary epithelium in vivo and in culture

“…2,[4][5][6]8 Ectopic expression of CDX2 is known to induce intestinal phenotypes such as MUC2 expression in Barrett's esophagus, and bile acid or chronic acid exposure was speculated to induce CDX2 expression in esophageal keratinocytes. 8,29 Inflammatory cytokines and infection may also induce CDX2 and then MUC2 expression.…”

“…8,29 Inflammatory cytokines and infection may also induce CDX2 and then MUC2 expression. 2,[4][5][6] For example, CDX2 expression was reportedly upregulated in cultured epithelial cells when they were infected with bacteria, and interactions of TLR with microbial components are involved in the regulation of MUC expression. [30][31][32][33][34][35] Therefore, bacterial components in bile may induce CDX2 expression and then aberrant MUC2 expression in the ducts.…”

“…2,4,5-8 CDX2-dependent intestinal metaplasia is noted in Barrett's esophagus with MUC2 expression, and bile acid and chronic acid exposure have been reported to induce CDX2 expression. 2,[4][5][6]8,9 Intestinal metaplasia is also involved in the pathogenesis of biliary diseases. For example, in chronic cholangitis such as hepatolithiasis, intestinal metaplasia with goblet cells occurs, and MUC2 is aberrantly expressed in goblet cells colocalized with CDX2.…”

“…Sixteen types of MUC have been identified. Intestinal metaplasia associated with the aberrant expression of MUC2 [1][2][3][4] is reportedly involved in tumorigenesis in several organs. Recent studies revealed that CDX2, a caudalrelated homeobox gene encoding an intestine-specific transcription factor, is a regulatory factor of intestinal development and expression of intestinal genes including MUC2 and is involved in intestinal metaplasia.…”