dc.date.accessioned | 2019-12-09T13:47:13Z | |
dc.date.available | 2019-12-09T13:47:13Z | |
dc.date.created | 2018-12-03T13:01:55Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Norum, Jens Henrik Skarpen, Ellen Brech, Andreas Kuiper, Raoul Waaler, Jo Krauss, Stefan Sørlie, Therese . The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology. Biological Research (Print). 2018, 51:3, 1-13 | |
dc.identifier.uri | http://hdl.handle.net/10852/71430 | |
dc.description.abstract | Background: The WNT pathway regulates intestinal stem cells and is frequently disrupted in intestinal adenomas. The pathway contains several potential biotargets for interference, including the poly-ADP ribosyltransferase enzymes tankyrase1 and 2. LGR5 is a known WNT pathway target gene and marker of intestinal stem cells. The LGR5+ stem cells are located in the crypt base and capable of regenerating all intestinal epithelial cell lineages.
Results: We treated Lgr5-EGFP-Ires-CreERT2;R26R-Confetti mice with the tankyrase inhibitor G007-LK for up to 3 weeks to assess the effect on duodenal stem cell homeostasis and on the integrity of intestinal epithelium. At the administered doses, G007-LK treatment inhibited WNT signalling in LGR5+ stem cells and reduced the number and distribution of cells traced from duodenal LGR5+ stem cells. However, the gross morphology of the duodenum remained unaltered and G007-LK-treated mice showed no signs of weight loss or any other visible morphological changes. The inhibitory effect on LGR5+ stem cell proliferation was reversible.
Conclusion: We show that the tankyrase inhibitor G007-LK is well tolerated by the mice, although proliferation of the LGR5+ intestinal stem cells was inhibited. Our observations suggest the presence of a tankyrase inhibitor-resistant cell population in the duodenum, able to rescue tissue integrity in the presence of G007-LK-mediated inhibition of the WNT signalling dependent LGR5+ intestinal epithelial stem cells. | en_US |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Norum, Jens Henrik | |
dc.creator.author | Skarpen, Ellen | |
dc.creator.author | Brech, Andreas | |
dc.creator.author | Kuiper, Raoul | |
dc.creator.author | Waaler, Jo | |
dc.creator.author | Krauss, Stefan | |
dc.creator.author | Sørlie, Therese | |
cristin.unitcode | 185,15,29,30 | |
cristin.unitname | Seksjon for fysiologi og cellebiologi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1638410 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Biological Research (Print)&rft.volume=51:3&rft.spage=1&rft.date=2018 | |
dc.identifier.jtitle | Biological Research (Print) | |
dc.identifier.volume | 51:3 | |
dc.identifier.startpage | 1 | |
dc.identifier.endpage | 13 | |
dc.identifier.doi | https://doi.org/10.1186/s40659-017-0151-6 | |
dc.identifier.urn | URN:NBN:no-74558 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0716-9760 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/71430/1/The%2Btankyrase%2Binhibitor%2BG007-LK-s40659-017-0151-6.pdf | |
dc.type.version | PublishedVersion | |