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Protection of the Peyer's patch‐associated crypt and villus epithelium against methotrexate‐induced damage is based on its distinct regulation of proliferation
Author(s) -
Renes Ingrid B.,
Verburg Melissa,
Bulsing Nathalie P.,
Ferdinandusse Sacha,
Büller Hans A.,
Dekker Jan,
Einerhand Alexandra W. C.
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1183
Subject(s) - crypt , epithelium , intestinal epithelium , enterocyte , biology , paneth cell , intestinal mucosa , apoptosis , goblet cell , gastrointestinal epithelium , cell growth , microbiology and biotechnology , small intestine , medicine , endocrinology , biochemistry , genetics
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. 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. Small intestinal segments containing PPs were excised after MTX treatment. Epithelial proliferation and apoptosis were assessed by detection of incorporated BrdU and cleaved caspase‐3, respectively. Epithelial functions were determined by the expression of cell type‐specific gene products at mRNA and protein level. Before and after MTX treatment, the number of BrdU‐positive cells was higher in PP crypts than in NP crypts. BrdU incorporation was diminished in NP crypts, while in PP crypts incorporation was hardly affected. In PP and NP crypts, similar and increased levels of cleaved caspase‐3‐positive cells were observed after MTX. 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 contrast, expression of the goblet cell markers, Muc2 and trefoil factor 3, and the Paneth cell marker, lysozyme, was maintained after MTX in both PP and NP epithelium. In conclusion, as MTX‐induced apoptosis was similar in PP and NP crypts, the protection of the PP epithelium seems to be based on differences in the regulation of epithelial proliferation. Enterocyte function in the PP epithelium was unaffected by MTX treatment. Goblet and Paneth cell function was maintained in both NP and PP epithelium. Copyright © 2002 John Wiley & Sons, Ltd.