FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385988511> ?p ?o ?g. }

• W4385988511 abstract "Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis.Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied. Gastric emptying of solids and volumes were determined by breath test and single-photon emission computed tomography, respectively. Gene expression was analyzed by RNA-sequencing, microarrays, immunoblotting, and immunofluorescence. Epigenetic assays included chromatin immunoprecipitation sequencing (13 targets), chromosome conformation capture sequencing, and reporter assays. Mechanistic studies used Cre-mediated recombination, RNA interference, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated epigenome editing.HIF1A signaling from physiological intracellular hypoxia was active in mouse and human NOS1+ myenteric neurons but reduced in diabetes. Deleting Hif1a in Nos1-expressing neurons reduced NOS1 protein by 50% to 92% and delayed gastric emptying of solids in female but not male mice. Stabilizing HIF1A with roxadustat (FG-4592), which is approved for human use, restored NOS1 and reversed gastroparesis in female diabetic mice. In nitrergic neurons, HIF1A up-regulated Nos1 transcription by binding and activating proximal and distal cis-regulatory elements, including newly discovered super-enhancers, facilitating RNA polymerase loading and pause-release, and by recruiting cohesin to loop anchors to alter chromosome topology.Pharmacologic HIF1A stabilization is a novel, translatable approach to restoring nitrergic signaling and treating diabetic gastroparesis. The newly recognized effects of HIF1A on chromosome topology may provide insights into physioxia- and ischemia-related organ function." @default.
• W4385988511 created "2023-08-19" @default.
• W4385988511 creator A5002025948 @default.
• W4385988511 creator A5003195595 @default.
• W4385988511 creator A5006544685 @default.
• W4385988511 creator A5009284315 @default.
• W4385988511 creator A5011567510 @default.
• W4385988511 creator A5014283643 @default.
• W4385988511 creator A5026563863 @default.
• W4385988511 creator A5029197610 @default.
• W4385988511 creator A5031123252 @default.
• W4385988511 creator A5033071737 @default.
• W4385988511 creator A5037552164 @default.
• W4385988511 creator A5042026897 @default.
• W4385988511 creator A5042784238 @default.
• W4385988511 creator A5044470070 @default.
• W4385988511 creator A5045243510 @default.
• W4385988511 creator A5046797792 @default.
• W4385988511 creator A5048820653 @default.
• W4385988511 creator A5050039580 @default.
• W4385988511 creator A5051245049 @default.
• W4385988511 creator A5051701943 @default.
• W4385988511 creator A5053182366 @default.
• W4385988511 creator A5073955320 @default.
• W4385988511 creator A5085481187 @default.
• W4385988511 creator A5085730035 @default.
• W4385988511 creator A5088634575 @default.
• W4385988511 creator A5090088048 @default.
• W4385988511 date "2023-08-01" @default.
• W4385988511 modified "2023-10-14" @default.
• W4385988511 title "Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice" @default.
• W4385988511 cites W1941076503 @default.
• W4385988511 cites W1972002559 @default.
• W4385988511 cites W1973062929 @default.
• W4385988511 cites W1980882515 @default.
• W4385988511 cites W2003206650 @default.
• W4385988511 cites W2003893456 @default.
• W4385988511 cites W2006187872 @default.
• W4385988511 cites W2017732224 @default.
• W4385988511 cites W2036781343 @default.
• W4385988511 cites W2038978204 @default.
• W4385988511 cites W2045959839 @default.
• W4385988511 cites W2058610977 @default.
• W4385988511 cites W2064210252 @default.
• W4385988511 cites W2065760418 @default.
• W4385988511 cites W2085743669 @default.
• W4385988511 cites W2090037708 @default.
• W4385988511 cites W2094148042 @default.
• W4385988511 cites W2097798909 @default.
• W4385988511 cites W2098134455 @default.
• W4385988511 cites W2102526923 @default.
• W4385988511 cites W2106893238 @default.
• W4385988511 cites W2112454216 @default.
• W4385988511 cites W2124058305 @default.
• W4385988511 cites W2136781148 @default.
• W4385988511 cites W2138899640 @default.
• W4385988511 cites W2143398582 @default.
• W4385988511 cites W2144941656 @default.
• W4385988511 cites W2148194696 @default.
• W4385988511 cites W2160516610 @default.
• W4385988511 cites W2195190137 @default.
• W4385988511 cites W2482792965 @default.
• W4385988511 cites W2596572267 @default.
• W4385988511 cites W2624675086 @default.
• W4385988511 cites W2788808640 @default.
• W4385988511 cites W2790188639 @default.
• W4385988511 cites W2793543956 @default.
• W4385988511 cites W2795707995 @default.
• W4385988511 cites W2801575631 @default.
• W4385988511 cites W2901273371 @default.
• W4385988511 cites W2964045421 @default.
• W4385988511 cites W3005328263 @default.
• W4385988511 cites W3089934761 @default.
• W4385988511 cites W3094079459 @default.
• W4385988511 cites W3111272930 @default.
• W4385988511 cites W3125397652 @default.
• W4385988511 cites W3135804864 @default.
• W4385988511 cites W4200231661 @default.
• W4385988511 cites W4205250458 @default.
• W4385988511 cites W4211130106 @default.
• W4385988511 cites W4281481726 @default.
• W4385988511 doi "https://doi.org/10.1053/j.gastro.2023.08.009" @default.
• W4385988511 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37597632" @default.
• W4385988511 hasPublicationYear "2023" @default.
• W4385988511 type Work @default.
• W4385988511 citedByCount "0" @default.
• W4385988511 crossrefType "journal-article" @default.
• W4385988511 hasAuthorship W4385988511A5002025948 @default.
• W4385988511 hasAuthorship W4385988511A5003195595 @default.
• W4385988511 hasAuthorship W4385988511A5006544685 @default.
• W4385988511 hasAuthorship W4385988511A5009284315 @default.
• W4385988511 hasAuthorship W4385988511A5011567510 @default.
• W4385988511 hasAuthorship W4385988511A5014283643 @default.
• W4385988511 hasAuthorship W4385988511A5026563863 @default.
• W4385988511 hasAuthorship W4385988511A5029197610 @default.
• W4385988511 hasAuthorship W4385988511A5031123252 @default.
• W4385988511 hasAuthorship W4385988511A5033071737 @default.
• W4385988511 hasAuthorship W4385988511A5037552164 @default.
• W4385988511 hasAuthorship W4385988511A5042026897 @default.
• W4385988511 hasAuthorship W4385988511A5042784238 @default.

• next