in the gastrointestinal tract is the epithelial layer and lamina propria of the small intestine and underlying mesenchymal stroma. The mammalian TGF-b family consists of three closely related members, designated TGF b1, b2 and b3, all of which are potent inhibitors of epithelial cell growth. These cytokines have been implicated in diverse phenomena including growth control, cell adhesion and motility, production of extracellular matrix components, and alteration of cell phenotype. TGF-b has been found to bind to several specific cell surface TGF-b receptors. TGF-b receptor is a serine/threonine kinase receptor complex that consists of two distinct transmembrane proteins known as type I and type II receptors. 
The type-1 and type-2 receptors work in a cooperative fashion; ligand binding to the type-1 receptor facilitates activation of the associated type-2 receptor, which then activates the intracellular signaling machine via SMAD proteins. Harsha et al have recently demonstrated that the use of Modulen, an immunomodulatory dietary supplement containing TGF-b, glutamine, and short chain fatty acids, provides a protective role against MTX-induced mucositis in a rat model. The authors showed that administration of formula supplemented with TGF-b provided statistically significant protection against weight loss, hypoalbuminemia, acidosis, and gastrointestinal damage following MTX administration. The authors hypothesized that Modulen supplementation resulted in one or more of the following: the protection of epithelial stem cells against MTX damage, leading to a larger mucosal stem cell Western blot In jejunum, Western blot analysis illustrated a significant decrease in p-ERK protein levels in MTX compared to control animals. These findings correlate with decreased rates of cell proliferation in MTX animals compared to control rats. Interestingly, b-catenin protein levels MSC1936369B increased in MTX rats compared to control animals. This finding may reflect the activated stem cell activity and may suggest the initiation of a regenerative process 72 hours after MTX-induced damage. Treatment with TGF-b resulted in a significant increase in b-catenin protein levels as compared to MTX and control rats. Bax protein levels increased significantly in MTX rats as compared to control rats and was correlated with elevated bax mRNA levels as well as with elevated rates of cell apoptosis following MTX administration. Treatment with TGF-b resulted in a significant decrease in bax protein levels compared to control and MTX rats. MTX animals have shown a significant decrease in IL-1B protein levels compared to control animals. Treatment with TGF-b resulted in a significant increase in IL-1B protein levels compared to MTX rats. In ileum, Western blot analysis illustrated a significant decrease in p-ERK protein, IL-1B protein and bcatenin protein levels in MTX rats compared to control animals. TGF-b2 Reduces MTX Induced Intestinal Injury population postregimen, increased regeneration during and after the regimen because of escape of mitotically-active cells from apoptosis, and the acceleration of regeneration after cessation of the MTX treatment. The purpose of the current study was to evaluate the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22210737 effect of TGF-b2 on enterocyte turnover during MTX-induced intestinal mucositis in a rat and in cell culture model. The molecular mechanisms underlying the dynamic processes of intestine-specific gene expression, cell fate determination, cellular differentiation and intestin