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IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NFκB-dependent manner

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Maleszewska, Monika, Moonen, Jan-Renier A.J., Huijkman, Nicolette, van de Sluis, Bart, Krenning, Guido, Harmsen, Martin C.·2013·Immunobiology
DOI 10.1016/j.imbio.2012.05.026
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Abstract

Endothelial to mesenchymal transition (EndMT) contributes to fibrotic diseases. The main inducer of EndMT is TGFβ signaling. TGFβ2 is the dominant isoform in the physiological embryonic EndMT, but its role in the pathological EndMT in the context of inflammatory co-stimulation is not known. The aim of this study was to investigate TGFβ2-induced EndMT in the context of inflammatory IL-1β signaling. Co-stimulation with IL-1β and TGFβ2, but not TGFβ1, caused synergistic induction of EndMT. Also, TGFβ2 was the only TGFβ isoform that was progressively upregulated during EndMT. External IL-1β stimulation was dispensable once EndMT was induced. The inflammatory transcription factor NFκB was upregulated in an additive manner by IL-1β and TGFβ2 co-stimulation. Co-stimulation also led to the nuclear translocation of NFκB which was sustained over long-term treatment. Activation of NFκB was indispensable for the co-induction of EndMT. Our data suggest that the microenvironment at the verge between inflammation (IL-1β) and tissue remodeling (TGFβ2) can strongly promote the process of EndMT. Therefore our findings provide new insights into the mechanisms of pathological EndMT.

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Metadata

Authors
Maleszewska, M., Moonen, J.-R. A. J., Huijkman, N., van de Sluis, B., Krenning, G., & Harmsen, M. C.
Venue
Immunobiology
Publisher
Elsevier BV
Published
2013-04
Volume
218
Issue
4
Pages
443-454
ISSN
0171-2985 (ISSN-L)
DOI
10.1016/j.imbio.2012.05.026
OpenAlex
W1981348175
Cited by
220
References
2
FWCI
3.02
Type
journal article
Language
en
Open access
hybrid
Licence
Funders
  • Dutch Government (FES0908)
  • Groningen University Institute for Drug Exploration (GUIDE)
  • ZonMW/NWO Innovational Research Incentive (916.11.022)
  • Jan Kornelis de Cock Foundation (JRM)

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CoChat. (2026). Citation check: IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NFκB-dependent manner. https://app.cochat.ai/papers/10.1016/j.imbio.2012.05.026
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Maleszewska, M., Moonen, J.-R. A. J., Huijkman, N., van de Sluis, B., Krenning, G., & Harmsen, M. C. (2013). IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NFκB-dependent manner. Immunobiology. https://doi.org/10.1016/j.imbio.2012.05.026

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