Graphic shows statistical differences in Gal-1 levels in in comparison with C57 mice for both muscles in the two analyzed ages (*= 0.0003 and 0.0001 for GA, 4-week-old and 9-week-old mice, respectively and *= 0.0031 and 0.0021 for DIA, 4-week-old and 9-week-old mice). with infiltrating CD45+ Btk inhibitor 1 R enantiomer hydrochloride leukocytes. By contrast, regenerating muscle tissue showed a marked decrease in Gal-1 to baseline levels. These results demonstrate significant regulation of Gal-1 expression in vivo and suggest a potential role for Gal-1 in muscle homeostasis and repair. mice Introduction Muscle degeneration, as found in genetic diseases such as Duchenne Muscular Dystrophy (DMD), results in significant morbidity and mortality worldwide. Specifically, DMD results from mutations in dystrophin, a component of the sarcolemmal complex that connects the actin cytoskeleton to the extracellular matrix. Muscle pathology ultimately results in progressive skeletal muscle wasting, leading to death in the second decade of life due to cardiac or respiratory failure (Blake et al. 2002; Emery 2002). Current treatment options fail to significantly reduce pathology, largely due to an incomplete understanding of the muscle degenerative and regenerative processes (Deconinck and Dan 2007; Radley et al. 2007). Several animal models are currently used in an effort to elucidate the mechanisms underlying DMD pathology. The murine model, the most commonly studied animal model of DMD, exhibits many key features of human DMD, including sarcolemmal instability, Ca2+ influx, myofiber apoptosis and necrosis, fibrosis, inflammation, and elevated serum creatinine kinase (CK) levels (Bulfield et al. 1984; Watchko et al. 2002; Collins and Morgan 2003). These features are intensified when the animals are submitted to compulsory physical activity (Brussee et al. 1997; Fraysse et al. 2004; De Luca et al. 2005). Importantly, regeneration, characterized by centrally localized nuclei, follows degeneration in the model, allowing studies of expression and localization of proteins putatively involved in degenerative and regenerative muscle processes (Blake et al. 2002; Watchko et al. 2002; Collins and Morgan 2003). Several studies implicate galectin-1 (Gal-1) in the development of skeletal muscle (Watt et al. 2004; Kami and Senba 2005). Gal-1 is a carbohydrate-binding protein expressed by many cells including myoblasts (Goldring, Jones, Thiagarajah, et al. 2002; Stowell, Arthur, et al. 2008). Gal-1 expression exhibits unique regulation during development; it is predominately expressed in the cytosol during myoblast stages, followed by peak expression and extracellular secretion, prior to fusion of myoblast into multinucleated muscle cells (Nowak et al. 1976; Barondes and Haywood-Reid 1981; Cooper and Barondes 1990; Harrison and Wilson 1992; Poirier et al. 1992; Watt et al. 2004). Gal-1 induces myoblast proliferation and fusion in vitro (Den Btk inhibitor 1 R enantiomer hydrochloride and Malinzak 1977; Gartner and Podleski 1975; Watt et al. 2004) and inhibits myoblast 71 integrin-mediated interactions with laminin (Cooper et al. 1991; Gu et al. 1994), suggesting that secretion of Gal-1 into the extracellular milieu may facilitate fusion in vivo. Consistent with a role for Gal-1 in initiating myoblast fusion, Gal-1-null mice show reduced myofiber formation in vivo (Watt et al. 2004; Georgiadis et al. 2007). In addition to putative roles of Gal-1 in muscle development, several studies suggest that Gal-1 may also mediate several aspects of muscle regeneration. Gal-1 induces dermal fibroblasts to express muscle-specific markers such as desmin (Goldring, Jones, Sewry, et al. 2002). Gal-1-null mice also experience impaired capacity to regenerate muscle tissue following injury (Watt et al. 2004; Vav1 Georgiadis et al. 2007). In addition, Gal-1 exhibits Btk inhibitor 1 R enantiomer hydrochloride a protective effect on tissue during damage, possibly through reducing the deleterious sequelae associated with inflammation (Rabinovich Btk inhibitor 1 R enantiomer hydrochloride et al. 2000). Indeed, Gal-1 induces the turnover of activated neutrophils, whose unchecked activity can damage viable tissue when not properly removed (Dias-Baruffi.