| dc.creator | Norum,Jens Henrik | |
| dc.creator | Skarpen,Ellen | |
| dc.creator | Brech,Andreas | |
| dc.creator | Kuiper,Raoul | |
| dc.creator | Waaler,Jo | |
| dc.creator | Krauss,Stefan | |
| dc.creator | Sørlie,Therese | |
| dc.date | 2018-01-01 | |
| dc.date.accessioned | 2019-05-02T21:22:41Z | |
| dc.date.available | 2019-05-02T21:22:41Z | |
| dc.identifier | https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100203 | |
| dc.identifier.uri | http://revistaschilenas.uchile.cl/handle/2250/82742 | |
| 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. | |
| dc.format | text/html | |
| dc.language | en | |
| dc.publisher | Sociedad de Biología de Chile | |
| dc.relation | 10.1186/s40659-017-0151-6 | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.source | Biological Research v.51 2018 | |
| dc.subject | Tankyrase inhibitor | |
| dc.subject | LGR5 | |
| dc.subject | WNT signalling | |
| dc.subject | Intestine | |
| dc.subject | Lineage tracing | |
| dc.subject | Stem cell | |
| dc.title | The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology | |
