Alterations in Epithelial and Mesenchymal Intestinal Gene Expression During Doxorubicin-Induced Mucositis in Mice |
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| Authors: | Barbara A E de Koning Dicky J Lindenbergh-Kortleve Rob Pieters Hans A Büller Ingrid B Renes Alexandra W C Einerhand |
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| Institution: | (1) Department of Pediatrics, Divisions of Pediatric Oncology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands;(2) Gastro-enterology and Nutrition, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands;(3) Neontaology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands;(4) Pediatric oncology and gastro-enterology, Erasmus MC-Sophia Children’s Hospital, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands |
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| Abstract: | In the current study we aimed to gain insight into epithelial-mesenchymal cross-talk and progenitor compartment modulation
during doxorubicin (DOX)-induced mucositis in mice. Intestinal segments were collected on various days after DOX treatment.
DOX-induced damage at day 1–2 was characterized by increased epithelial proliferation and apoptosis and a decrease in the
expression of epithelial differentiation markers. Concurrently, T-cell factor-4 (TCF4) levels increased and the epithelial
differentiation enhancing factor, bone morphogenic protein-4 (BMP4), decreased. During severe damage (day 3), BMP4 levels
were significantly increased, which inversely correlated with epithelial proliferation. At the same time, the expression of
the epithelial differentiation markers was increasing again. At day 7, BMP4 levels were down-regulated, while the levels of
the epithelial differentiation markers and TCF4 were normalized again. These data suggest that in response to DOX-induced
damage, BMP4 and TCF4 are modulated in such a way that homeostasis of the progenitor compartment is partly preserved. |
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| Keywords: | Morphogens Intestinal differentiation Epithelial homeostasis Bone morphogenetic proteins TCF4 |
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