Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283076178> ?p ?o ?g. }
- W4283076178 endingPage "1130" @default.
- W4283076178 startingPage "1119" @default.
- W4283076178 abstract "To investigate how the mucosal barrier in the intestine influences the development of arthritis, considering that metabolic changes in the intestinal epithelium influence its barrier function.Intestinal hypoxia inducible factor (HIF)-2α expression was assessed before, at onset and during experimental arthritis and human rheumatoid arthritis (RA). Intestinal epithelial cell-specific HIF2α conditional knock-out mice were generated (HIF2α∆IEC) and subjected to collagen-induced arthritis. Clinical and histological courses of arthritis were recorded; T-cell and B-cell subsets were analysed in the gut and secondary lymphatic organs; and intestinal epithelial cells were subjected to molecular mRNA sequencing in HIF2α∆IEC and littermate control mice. The gut intestinal HIF2α target genes were delineated by chromatin immunoprecipitation and luciferase experiments. Furthermore, pharmacological HIF2α inhibitor PT2977 was used for inhibition of arthritis.Intestinal HIF2α expression peaked at onset of experimental arthritis and RA. Conditionally, deletion of HIF2α in gut epithelial cells inhibited arthritis and was associated with improved intestinal barrier function and less intestinal and lymphatic Th1 and Th17 activation. Mechanistically, HIF2α induced the transcription of the pore-forming claudin (CLDN)-15, which inhibits intestinal barrier integrity. Furthermore, treatment with HIF2α inhibitor decreased claudin-15 expression in epithelial cells and inhibited arthritis.These findings show that the HIF2α-CLDN15 axis is critical for the breakdown of intestinal barrier function at onset of arthritis, highlighting the functional link between intestinal homeostasis and arthritis." @default.
- W4283076178 created "2022-06-19" @default.
- W4283076178 creator A5013964825 @default.
- W4283076178 creator A5018434374 @default.
- W4283076178 creator A5019233591 @default.
- W4283076178 creator A5020328511 @default.
- W4283076178 creator A5023335489 @default.
- W4283076178 creator A5027366590 @default.
- W4283076178 creator A5038906848 @default.
- W4283076178 creator A5040094332 @default.
- W4283076178 creator A5044176546 @default.
- W4283076178 creator A5048360103 @default.
- W4283076178 creator A5054546022 @default.
- W4283076178 creator A5072082129 @default.
- W4283076178 creator A5075261558 @default.
- W4283076178 creator A5075263979 @default.
- W4283076178 creator A5078490704 @default.
- W4283076178 creator A5081328906 @default.
- W4283076178 date "2022-06-16" @default.
- W4283076178 modified "2023-10-16" @default.
- W4283076178 title "Epithelial HIF2α expression induces intestinal barrier dysfunction and exacerbation of arthritis" @default.
- W4283076178 cites W1701869895 @default.
- W4283076178 cites W1965157206 @default.
- W4283076178 cites W1987331979 @default.
- W4283076178 cites W1992152055 @default.
- W4283076178 cites W2012422301 @default.
- W4283076178 cites W2024654129 @default.
- W4283076178 cites W2027121745 @default.
- W4283076178 cites W2034066083 @default.
- W4283076178 cites W2048998174 @default.
- W4283076178 cites W2075468859 @default.
- W4283076178 cites W2103137874 @default.
- W4283076178 cites W2113368377 @default.
- W4283076178 cites W2122498073 @default.
- W4283076178 cites W2123248918 @default.
- W4283076178 cites W2131691531 @default.
- W4283076178 cites W2136967594 @default.
- W4283076178 cites W2138899640 @default.
- W4283076178 cites W2147160899 @default.
- W4283076178 cites W2156904705 @default.
- W4283076178 cites W2166710590 @default.
- W4283076178 cites W2281990250 @default.
- W4283076178 cites W2464915778 @default.
- W4283076178 cites W2514212469 @default.
- W4283076178 cites W2734036824 @default.
- W4283076178 cites W2749177495 @default.
- W4283076178 cites W2778082937 @default.
- W4283076178 cites W2784023062 @default.
- W4283076178 cites W2886363262 @default.
- W4283076178 cites W2892759967 @default.
- W4283076178 cites W2897708219 @default.
- W4283076178 cites W2901898635 @default.
- W4283076178 cites W2940220885 @default.
- W4283076178 cites W2953812088 @default.
- W4283076178 cites W2955214382 @default.
- W4283076178 cites W2979199018 @default.
- W4283076178 cites W2986330148 @default.
- W4283076178 cites W2995371419 @default.
- W4283076178 cites W3019025224 @default.
- W4283076178 cites W3095423161 @default.
- W4283076178 cites W3134475720 @default.
- W4283076178 cites W4247197718 @default.
- W4283076178 doi "https://doi.org/10.1136/annrheumdis-2021-222035" @default.
- W4283076178 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35710307" @default.
- W4283076178 hasPublicationYear "2022" @default.
- W4283076178 type Work @default.
- W4283076178 citedByCount "3" @default.
- W4283076178 countsByYear W42830761782023 @default.
- W4283076178 crossrefType "journal-article" @default.
- W4283076178 hasAuthorship W4283076178A5013964825 @default.
- W4283076178 hasAuthorship W4283076178A5018434374 @default.
- W4283076178 hasAuthorship W4283076178A5019233591 @default.
- W4283076178 hasAuthorship W4283076178A5020328511 @default.
- W4283076178 hasAuthorship W4283076178A5023335489 @default.
- W4283076178 hasAuthorship W4283076178A5027366590 @default.
- W4283076178 hasAuthorship W4283076178A5038906848 @default.
- W4283076178 hasAuthorship W4283076178A5040094332 @default.
- W4283076178 hasAuthorship W4283076178A5044176546 @default.
- W4283076178 hasAuthorship W4283076178A5048360103 @default.
- W4283076178 hasAuthorship W4283076178A5054546022 @default.
- W4283076178 hasAuthorship W4283076178A5072082129 @default.
- W4283076178 hasAuthorship W4283076178A5075261558 @default.
- W4283076178 hasAuthorship W4283076178A5075263979 @default.
- W4283076178 hasAuthorship W4283076178A5078490704 @default.
- W4283076178 hasAuthorship W4283076178A5081328906 @default.
- W4283076178 hasConcept C126322002 @default.
- W4283076178 hasConcept C142724271 @default.
- W4283076178 hasConcept C203014093 @default.
- W4283076178 hasConcept C2777077863 @default.
- W4283076178 hasConcept C2781077229 @default.
- W4283076178 hasConcept C3019368612 @default.
- W4283076178 hasConcept C51911345 @default.
- W4283076178 hasConcept C529295009 @default.
- W4283076178 hasConcept C71924100 @default.
- W4283076178 hasConcept C86803240 @default.
- W4283076178 hasConcept C95444343 @default.
- W4283076178 hasConceptScore W4283076178C126322002 @default.
- W4283076178 hasConceptScore W4283076178C142724271 @default.