Alterations in epithelial and mesenchymal intestinal gene expression during doxorubicin-induced mucositis in mice.
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.
de Koning
Barbara A E
BA
Department of Pediatrics, Divisions of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. b.dekoning@erasmusmc.nl
Lindenbergh-Kortleve
Dicky J
DJ
Pieters
Rob
R
Büller
Hans A
HA
Renes
Ingrid B
IB
Einerhand
Alexandra W C
AW
D000818:Animals; D017209:Apoptosis; D019485:Bone Morphogenetic Proteins / Q000032:analysis*; D002455:Cell Division; D004317:Doxorubicin / Q000009:adverse effects*; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D015870:Gene Expression; D006706:Homeostasis / Q000502:physiology; D007413:Intestinal Mucosa / Q000737:chemistry*; D008297:Male; D008648:Mesoderm / Q000737:chemistry / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D052016:Mucositis / Q000139:chemically induced* / Q000473:pathology; D020239:Receptor Cross-Talk / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D004317:Doxorubicin