Matches in SemOpenAlex for { <https://semopenalex.org/work/W4293037955> ?p ?o ?g. }
- W4293037955 abstract "ABSTRACT Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have previously reported that ureteric bud-specific ablation of the gene expressing the exocyst subunit EXOC5 in late murine gestation results in failure of urothelial stratification, cell death and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-κB stress response. Impaired autophagy first provokes canonical NF-κB activity, which is progressively followed by increasing levels of non-canonical NF-κB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of the pan-caspase inhibitor z-VAD-FMK at embryonic day 16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-κB signaling, which promotes obstructive uropathy." @default.
- W4293037955 created "2022-08-25" @default.
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- W4293037955 date "2022-10-01" @default.
- W4293037955 modified "2023-10-15" @default.
- W4293037955 title "Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling" @default.
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- W4293037955 doi "https://doi.org/10.1242/dmm.049785" @default.
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