Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387172372> ?p ?o ?g. }
- W4387172372 abstract "Inflammation-associated fibroblasts (IAFs) are associated with the progression and drug resistance of chronic inflammatory diseases such as inflammatory bowel disease (IBD), but their direct impact on epithelial function and architecture is unknown. In this study, we developed an in vitro model whereby human colon fibroblasts are induced to become IAFs by specific cytokines and recapitulate key features of IAFs in vivo . When co-cultured with patient-derived colon organoids (colonoids), IAFs induced rapid colonoid swelling and barrier disruption due to swelling and rupture of individual epithelial cells. Epithelial cells co-cultured with IAFs also exhibit increased DNA damage, mitotic errors, and proliferation arrest. These IAF-induced epithelial defects are mediated through a paracrine pathway involving prostaglandin E2 (PGE2) and the PGE2 receptor EP4, leading to PKA-dependent activation of the CFTR chloride channel. Importantly, EP4-specific chemical inhibitors effectively prevented colonoid swelling and restored normal proliferation and genome stability of IAF-exposed epithelial cells. These findings reveal a mechanism by which IAFs could promote and perpetuate IBD and suggest a potential treatment to mitigate inflammation-associated epithelial injury.Inflammation-associated fibroblasts compromise colon epithelial barrier integrity and genome stability via PGE2-EP4 signaling." @default.
- W4387172372 created "2023-09-30" @default.
- W4387172372 creator A5004681741 @default.
- W4387172372 creator A5018557213 @default.
- W4387172372 creator A5031543598 @default.
- W4387172372 creator A5034572569 @default.
- W4387172372 creator A5034601651 @default.
- W4387172372 creator A5042275051 @default.
- W4387172372 creator A5043861768 @default.
- W4387172372 creator A5044478621 @default.
- W4387172372 creator A5044859707 @default.
- W4387172372 creator A5064017939 @default.
- W4387172372 creator A5068013365 @default.
- W4387172372 creator A5075294015 @default.
- W4387172372 creator A5081222516 @default.
- W4387172372 creator A5081919864 @default.
- W4387172372 creator A5082505578 @default.
- W4387172372 date "2023-09-29" @default.
- W4387172372 modified "2023-10-18" @default.
- W4387172372 title "Disruption of Epithelium Integrity by Inflammation-Associated Fibroblasts through Prostaglandin Signaling" @default.
- W4387172372 cites W1483496013 @default.
- W4387172372 cites W1510122008 @default.
- W4387172372 cites W1638694981 @default.
- W4387172372 cites W1964636123 @default.
- W4387172372 cites W1965157206 @default.
- W4387172372 cites W2002513358 @default.
- W4387172372 cites W2024346860 @default.
- W4387172372 cites W2025482435 @default.
- W4387172372 cites W2027824704 @default.
- W4387172372 cites W2030542406 @default.
- W4387172372 cites W2053425043 @default.
- W4387172372 cites W2054477373 @default.
- W4387172372 cites W2056548679 @default.
- W4387172372 cites W2058036222 @default.
- W4387172372 cites W2059747767 @default.
- W4387172372 cites W2103567384 @default.
- W4387172372 cites W2106379906 @default.
- W4387172372 cites W2115934424 @default.
- W4387172372 cites W2116823408 @default.
- W4387172372 cites W2122054926 @default.
- W4387172372 cites W2123511827 @default.
- W4387172372 cites W2123673215 @default.
- W4387172372 cites W2127903487 @default.
- W4387172372 cites W2129935236 @default.
- W4387172372 cites W2143625465 @default.
- W4387172372 cites W2150396480 @default.
- W4387172372 cites W2151829259 @default.
- W4387172372 cites W2168654564 @default.
- W4387172372 cites W2308998098 @default.
- W4387172372 cites W2313572017 @default.
- W4387172372 cites W2324559253 @default.
- W4387172372 cites W2346861401 @default.
- W4387172372 cites W2462025033 @default.
- W4387172372 cites W2534981832 @default.
- W4387172372 cites W2564267981 @default.
- W4387172372 cites W2572585639 @default.
- W4387172372 cites W2593695507 @default.
- W4387172372 cites W2749121018 @default.
- W4387172372 cites W2798114557 @default.
- W4387172372 cites W2800418484 @default.
- W4387172372 cites W2800993925 @default.
- W4387172372 cites W2879376898 @default.
- W4387172372 cites W2891496794 @default.
- W4387172372 cites W2893059410 @default.
- W4387172372 cites W2894232765 @default.
- W4387172372 cites W2900505395 @default.
- W4387172372 cites W2903937690 @default.
- W4387172372 cites W2911274716 @default.
- W4387172372 cites W2917423992 @default.
- W4387172372 cites W2935762014 @default.
- W4387172372 cites W2954675852 @default.
- W4387172372 cites W2955382865 @default.
- W4387172372 cites W2963622568 @default.
- W4387172372 cites W2970463661 @default.
- W4387172372 cites W2988615929 @default.
- W4387172372 cites W2991882421 @default.
- W4387172372 cites W2998926895 @default.
- W4387172372 cites W3003058300 @default.
- W4387172372 cites W3014730061 @default.
- W4387172372 cites W3044545672 @default.
- W4387172372 cites W3093148868 @default.
- W4387172372 cites W3104645826 @default.
- W4387172372 cites W3109793392 @default.
- W4387172372 cites W3110852430 @default.
- W4387172372 cites W3111853778 @default.
- W4387172372 cites W3126673609 @default.
- W4387172372 cites W3154301139 @default.
- W4387172372 cites W3161368393 @default.
- W4387172372 cites W3163348136 @default.
- W4387172372 cites W3164692211 @default.
- W4387172372 cites W3178186466 @default.
- W4387172372 cites W3202649987 @default.
- W4387172372 cites W3213716835 @default.
- W4387172372 cites W4206395681 @default.
- W4387172372 cites W4210410309 @default.
- W4387172372 cites W4230633180 @default.
- W4387172372 cites W4243431867 @default.
- W4387172372 cites W4318755347 @default.
- W4387172372 cites W4319295205 @default.
- W4387172372 cites W4366249637 @default.