Itt, Xia, et al. 1998; Houzelstein et al. 2008). As a result, whereas most mammalian species, including humans, have a single Lgals4 gene, only mice have two paralogues. Like each tandem-repeat galectin in vertebrates, galectin-4 and -6 contain two CRDs joined by a linker area (Gitt, Xia, et al. 1998; Houzelstein et al. 2004). Also, as they have as a great deal as 83 identity in the amino-acid level (Gitt, Colnot, et al. 1998), these two proteins are probably to become, at the least partially, functionally redundant. The Lgals6 gene evolution, nevertheless, has been affected by an episode of constructive selection that prompted its divergence from Lgals4 and contributed to the accumulation of differences inside the galectin-6 linker and its flanking regions too as in its C-terminal CRD (Houzelstein et al. 2008). Galectin-6 might, hence, have also developed a number of new properties (neofunctionalization). Positive choice facilitates the fixation of alleles under choice. The Lgals4Lgals6 locus, on the other hand, continues to be polymorphic, each in wild-type populations and in laboratory mouse strains. As an illustration, whereas some mice, which include the 129/Sv laboratory strain, carry the Lgals4-Lgals6 gene duplication, others, like the C57BL/6J laboratory strain, carry only the unduplicated Lgals4 gene (Houzelstein et al. 2008). Absolutely nothing is recognized with regards to the part galectin-6 might play, whereas galectin-4 (initially known as L36; Leffler et al. 1989; Oda et al. 1993) has been investigated inside a quantity of studies. Galectin-4 is expressed pretty much exclusively inside the digestive tract. It was initially identified as an adherens junction protein expressed in the tongue epithelium from the pig (Chiu et al. 1992; Chiu et al. 1994). It has also been shown to become a significant component of lipid rafts in brush border membranes of your pig little intestine epithelial cells (reviewed in Danielsen and Hansen 2008). In cultures of human enterocyte-like HT-29 cells, galectin-4 binds to and recruits the apical glycoproteins in detergent-resistant membranes (Delacour et al. 2005; Morelle et al. 2009; Stechly et al. 2009). In cell cultures, galectin-4 is secreted both apically and, to a lesser extent, basolaterally (Stechly et al. 2009). Galectin-4 has been connected using a quantity of problems. Its expression is altered in many gastrointestinal cancers (Rechreche et al.Resorufin custom synthesis 1997; Hippo et al.FX1 In stock 2001; Nagy et al. 2003; Huflejt and Leffler 2004; van Baal et al. 2005; Rumilla et al. 2006; Duerr et al. 2008; Balan et al. 2010). Some authors suggested that it not simply may perhaps have the properties of a tumor progression marker (Watanabe et al. 2011)349 but additionally may function as a tumor suppressor in human colorectal cancer (Satelli et al.PMID:23891445 2011). Various research have also implicated galectin-4 inside the inflammatory response, though with conflicting conclusions. Some concluded that galectin-4 stimulates T-cells to make interleukin-6 and contributes to the development of inflammatory bowel illness (Hokama et al. 2004). Other folks concluded that galectin-4 induces apoptosis of mucosal T-cells and promotes resolution on the inflammatory response (Paclik, Danese, et al. 2008; Paclik et al. 2011). The cause for these discrepancies is still unknown (reviewed in Liu and Rabinovich 2010). Galectin-4 has also been involved in intestinal epithelial wound healing (Paclik, Lohse, et al. 2008) and in the killing of human blood group antigen-expressing Escherichia coli present inside the intestinal lumen (Stowell et al. 201.