The enterocyte markers, sucrase-isomaltase, sodium-glucose co-transporter 1, glucose transporters 2 and 5, and intestinal and liver fatty acid binding protein, were down-regulated after MTX in NP epithelium but not in PP epithelium. In PP and NP crypts, similar and increased levels of cleaved caspase-3-positive cells were observed after MTX. BrdU incorporation was diminished in NP crypts, while in PP crypts incorporation was hardly affected. Before and after MTX treatment, the number of BrdU-positive cells was higher in PP crypts than in NP crypts. Epithelial functions were determined by the expression of cell type-specific gene products at mRNA and protein level. Epithelial proliferation and apoptosis were assessed by detection of incorporated BrdU and cleaved caspase-3, respectively. Small intestinal segments containing PPs were excised after MTX treatment. To assess the mechanism(s) preventing damage to the PP epithelium after MTX treatment, epithelial proliferation, apoptosis, and cell functions were studied in a rat-MTX model. The crypt and villus epithelium associated with Peyer's patches (PPs) is largely spared from methotrexate (MTX)-induced damage, compared with the non-patch (NP) epithelium.

Dark crypt tc