FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2117765445> ?p ?o ?g. }

• W2117765445 endingPage "268.e8" @default.
• W2117765445 startingPage "259" @default.
• W2117765445 abstract "Background & AimsDkk1 is a secreted antagonist of the Wnt/β-catenin signaling pathway. It is induced by inflammatory cytokines during colitis and exacerbates tissue damage by promoting apoptosis of epithelial cells. However, little is known about the physiologic role of Dkk1 in normal intestinal homeostasis and during wound repair following mucosal injury. We investigated whether inhibition of Dkk1 affects the morphology and function of the adult intestine.MethodsWe used doubleridge mice (Dkk1d/d), which have reduced expression of Dkk1, and an inhibitory Dkk1 antibody to modulate Wnt/β-catenin signaling in the intestine. Intestinal inflammation was induced with dextran sulfate sodium (DSS), followed by a recovery period in which mice were given regular drinking water. Animals were killed before, during, or after DSS administration; epithelial homeostasis and the activity of major signaling pathways were investigated by morphometric analysis, bromo-2′-deoxyuridine incorporation, and immunostaining.ResultsReduced expression of Dkk1 increased proliferation of epithelial cells and lengthened crypts in the large intestine, which was associated with increased transcriptional activity of β-catenin. Crypt extension was particularly striking when Dkk1 was inhibited during acute colitis. Dkk1d/d mice recovered significantly faster from intestinal inflammation but exhibited crypt architectural irregularities and epithelial hyperproliferation compared with wild-type mice. Survival signaling pathways were concurrently up-regulated in Dkk1d/d mice, including the AKT/β-catenin, ERK/Elk-1, and c-Jun pathways.ConclusionsDkk1, an antagonist of Wnt/β-catenin signaling, regulates intestinal epithelial homeostasis under physiologic conditions and during inflammation. Depletion of Dkk1 induces a strong proliferative response that promotes wound repair after colitis. Dkk1 is a secreted antagonist of the Wnt/β-catenin signaling pathway. It is induced by inflammatory cytokines during colitis and exacerbates tissue damage by promoting apoptosis of epithelial cells. However, little is known about the physiologic role of Dkk1 in normal intestinal homeostasis and during wound repair following mucosal injury. We investigated whether inhibition of Dkk1 affects the morphology and function of the adult intestine. We used doubleridge mice (Dkk1d/d), which have reduced expression of Dkk1, and an inhibitory Dkk1 antibody to modulate Wnt/β-catenin signaling in the intestine. Intestinal inflammation was induced with dextran sulfate sodium (DSS), followed by a recovery period in which mice were given regular drinking water. Animals were killed before, during, or after DSS administration; epithelial homeostasis and the activity of major signaling pathways were investigated by morphometric analysis, bromo-2′-deoxyuridine incorporation, and immunostaining. Reduced expression of Dkk1 increased proliferation of epithelial cells and lengthened crypts in the large intestine, which was associated with increased transcriptional activity of β-catenin. Crypt extension was particularly striking when Dkk1 was inhibited during acute colitis. Dkk1d/d mice recovered significantly faster from intestinal inflammation but exhibited crypt architectural irregularities and epithelial hyperproliferation compared with wild-type mice. Survival signaling pathways were concurrently up-regulated in Dkk1d/d mice, including the AKT/β-catenin, ERK/Elk-1, and c-Jun pathways. Dkk1, an antagonist of Wnt/β-catenin signaling, regulates intestinal epithelial homeostasis under physiologic conditions and during inflammation. Depletion of Dkk1 induces a strong proliferative response that promotes wound repair after colitis." @default.
• W2117765445 created "2016-06-24" @default.
• W2117765445 creator A5030624991 @default.
• W2117765445 creator A5042841599 @default.
• W2117765445 creator A5048920581 @default.
• W2117765445 creator A5051956542 @default.
• W2117765445 creator A5052140012 @default.
• W2117765445 creator A5069460640 @default.
• W2117765445 creator A5074708797 @default.
• W2117765445 creator A5091773220 @default.
• W2117765445 date "2011-07-01" @default.
• W2117765445 modified "2023-10-14" @default.
• W2117765445 title "The Wnt Antagonist Dkk1 Regulates Intestinal Epithelial Homeostasis and Wound Repair" @default.
• W2117765445 cites W1541209562 @default.
• W2117765445 cites W1564357553 @default.
• W2117765445 cites W1967026374 @default.
• W2117765445 cites W1968304762 @default.
• W2117765445 cites W1993677820 @default.
• W2117765445 cites W1999966222 @default.
• W2117765445 cites W2000159893 @default.
• W2117765445 cites W2004998891 @default.
• W2117765445 cites W2017632960 @default.
• W2117765445 cites W2021370278 @default.
• W2117765445 cites W2023407460 @default.
• W2117765445 cites W2031352506 @default.
• W2117765445 cites W2048471338 @default.
• W2117765445 cites W2063731747 @default.
• W2117765445 cites W2069916625 @default.
• W2117765445 cites W2084763423 @default.
• W2117765445 cites W2087251699 @default.
• W2117765445 cites W2089449927 @default.
• W2117765445 cites W2092642151 @default.
• W2117765445 cites W2093947855 @default.
• W2117765445 cites W2100295977 @default.
• W2117765445 cites W2100768553 @default.
• W2117765445 cites W2114769013 @default.
• W2117765445 cites W2117156715 @default.
• W2117765445 cites W2121370170 @default.
• W2117765445 cites W2125311914 @default.
• W2117765445 cites W2125419124 @default.
• W2117765445 cites W2128444087 @default.
• W2117765445 cites W2140992718 @default.
• W2117765445 cites W2155170442 @default.
• W2117765445 cites W2158734690 @default.
• W2117765445 cites W2160664367 @default.
• W2117765445 cites W2163169815 @default.
• W2117765445 cites W2166862263 @default.
• W2117765445 cites W2167234458 @default.
• W2117765445 cites W4292198229 @default.
• W2117765445 doi "https://doi.org/10.1053/j.gastro.2011.03.043" @default.
• W2117765445 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3551610" @default.
• W2117765445 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21440550" @default.
• W2117765445 hasPublicationYear "2011" @default.
• W2117765445 type Work @default.
• W2117765445 sameAs 2117765445 @default.
• W2117765445 citedByCount "110" @default.
• W2117765445 countsByYear W21177654452012 @default.
• W2117765445 countsByYear W21177654452013 @default.
• W2117765445 countsByYear W21177654452014 @default.
• W2117765445 countsByYear W21177654452015 @default.
• W2117765445 countsByYear W21177654452016 @default.
• W2117765445 countsByYear W21177654452017 @default.
• W2117765445 countsByYear W21177654452018 @default.
• W2117765445 countsByYear W21177654452019 @default.
• W2117765445 countsByYear W21177654452020 @default.
• W2117765445 countsByYear W21177654452021 @default.
• W2117765445 countsByYear W21177654452022 @default.
• W2117765445 countsByYear W21177654452023 @default.
• W2117765445 crossrefType "journal-article" @default.
• W2117765445 hasAuthorship W2117765445A5030624991 @default.
• W2117765445 hasAuthorship W2117765445A5042841599 @default.
• W2117765445 hasAuthorship W2117765445A5048920581 @default.
• W2117765445 hasAuthorship W2117765445A5051956542 @default.
• W2117765445 hasAuthorship W2117765445A5052140012 @default.
• W2117765445 hasAuthorship W2117765445A5069460640 @default.
• W2117765445 hasAuthorship W2117765445A5074708797 @default.
• W2117765445 hasAuthorship W2117765445A5091773220 @default.
• W2117765445 hasBestOaLocation W21177654451 @default.
• W2117765445 hasConcept C126322002 @default.
• W2117765445 hasConcept C134018914 @default.
• W2117765445 hasConcept C137620995 @default.
• W2117765445 hasConcept C203014093 @default.
• W2117765445 hasConcept C2775862500 @default.
• W2117765445 hasConcept C2776914184 @default.
• W2117765445 hasConcept C2777491412 @default.
• W2117765445 hasConcept C2780269544 @default.
• W2117765445 hasConcept C3019368612 @default.
• W2117765445 hasConcept C502942594 @default.
• W2117765445 hasConcept C62478195 @default.
• W2117765445 hasConcept C63645605 @default.
• W2117765445 hasConcept C71924100 @default.
• W2117765445 hasConcept C86803240 @default.
• W2117765445 hasConcept C95444343 @default.
• W2117765445 hasConceptScore W2117765445C126322002 @default.
• W2117765445 hasConceptScore W2117765445C134018914 @default.
• W2117765445 hasConceptScore W2117765445C137620995 @default.
• W2117765445 hasConceptScore W2117765445C203014093 @default.
• W2117765445 hasConceptScore W2117765445C2775862500 @default.

• next