Immunohistochemical Characterization of the Distribution of Galectin-4 in Porcine Small Intestine

Abstract

Galectins are an evolutionarily conserved family of 15 different lectins found in various combinations in virtually every type of animal cell. One of the primary galectins expressed in intestinal epithelium is galectin-4, a tandem-repeat galectin with two carbohydrate-recognition domains in a single polypeptide chain. In the current study, we produced an anti-galectin-4 monoclonal antibody (MAb) for determining the distribution of galectin-4 in porcine small intestine to enhance our understanding of where galectin-4 performs its functions in the small intestine. In immunohistochemistry studies, this MAb detected galectin-4 primarily in the cytoplasm of absorptive epithelial cells lining intestinal villi. Mature epithelial cells at the villous tips stained the most intensely with this MAb, with progressively less intense staining observed along the sides of villi and into the crypts. In addition to its cytoplasmic localization, galectin-4 was also associated with nuclei in villous tip cells, indicating that some galectin-4 may migrate to the nucleus during terminal maturation of these cells. In intestinal crypts, a specific subset of cells, which may be enteroendocrine cells, expressed galectin-4 at a relatively high level. Galectin-4 distribution patterns were similar in all three regions (duodenum, jejunum, and ileum) of porcine small intestine.

Galectin‐4 functions as a tumor suppressor of human colorectal cancer

“…Multiple studies have identified mutations in the well-characterized APC, K-Ras, p53 , ß-catenin, axin, EGFR, as well as uncharacterized genes whose function is yet to be established in predisposition to the majority of CRC 3. Although gal-4 mRNA is highly restricted to the gastrointestinal tract6, 7, its translation and function in colonic epithelia or consequences of its loss of expression in CRC remains unknown. Our immunohistochemical analyses clearly indicated that gal-4 was highly expressed in the epithelial lining of the normal human colon crypts, which was greatly reduced in adenomas and, nearly absent in invasive carcinomas.…”

“…The facts that galectins share only partial amino acid sequence homology and certain galectins are uniquely expressed in a tissue-dependent manner raise a strong possibility that each galectin possesses a specific cellular function. For instance, galectin-4 (gal-4), a 323-amino acid (36 kDa) protein, is predominantly expressed in the luminal epithelia of the gastrointestinal tract6, 7. However, gal-4 was also detected in liver, breast, ovary and other tissues, which was up-regulated in the corresponding cancers8-11.…”

Innate immune lectins kill bacteria expressing blood group antigen

“…Previous studies demonstrated high levels of galectin expression in the intestinal mucosa where they may serve as pathogen recognition proteins13,14, suggesting Gal-3, Gal-4, and Gal-8 may facilitate innate immunity toward BG B + pathogens. While previous studies have shown that several innate immune lectins can directly affect pathogen viability3,15,16, including potential roles for galectins in pathogen adhesion, recognition, and killing14, there is no direct evidence as to whether galectins can alter prokaryote viability.…”

Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

“…[12][13][14][15][16] A total of 15 different galectins are known (reviewed by Liu 17 ), and among these, galectin-4 (gal-4), the protein of interest in this study, is a 323-amino acid (36 kDa) protein with two carbohydrate recognition domains, one on each end of the molecule, and its expression is predominantly restricted to the epithelial cells of the colorectal luminal layer. 18,19 We have previously demonstrated that the intracellular gal-4 interacts with β-catenin resulting in down-regulation of Wnt-signaling pathwaymediated cell proliferation. 12 Others have also made similar observations.…”